{"id":995,"date":"2021-08-23T17:11:54","date_gmt":"2021-08-23T15:11:54","guid":{"rendered":"https:\/\/wordpress-test.app.u-pariscite.fr\/who-am-i\/?page_id=995"},"modified":"2021-08-23T17:11:54","modified_gmt":"2021-08-23T15:11:54","slug":"integrity-in-response-to-stress-and-challenge","status":"publish","type":"page","link":"https:\/\/wordpress-test.app.u-pariscite.fr\/who-am-i\/en\/integrity-in-response-to-stress-and-challenge\/","title":{"rendered":"Integrity in response to stress and challenge"},"content":{"rendered":"

[et_pb_section bb_built=\u00a0\u00bb1″ next_background_color=\u00a0\u00bb#000000″ inner_width=\u00a0\u00bbauto\u00a0\u00bb inner_max_width=\u00a0\u00bbnone\u00a0\u00bb][et_pb_row][et_pb_column type=\u00a0\u00bb4_4″][et_pb_post_title admin_label=\u00a0\u00bbTitre de la page\u00a0\u00bb _builder_version=\u00a0\u00bb3.22.1″ meta=\u00a0\u00bboff\u00a0\u00bb featured_image=\u00a0\u00bboff\u00a0\u00bb \/][\/et_pb_column][\/et_pb_row][et_pb_row][et_pb_column type=\u00a0\u00bb3_4″][et_pb_text admin_label=\u00a0\u00bbIntro\u00a0\u00bb _builder_version=\u00a0\u00bb3.22.1″ module_id=\u00a0\u00bbintro\u00a0\u00bb text_text_shadow_horizontal_length=\u00a0\u00bbtext_text_shadow_style,%91object Object%93″ text_text_shadow_vertical_length=\u00a0\u00bbtext_text_shadow_style,%91object Object%93″ text_text_shadow_blur_strength=\u00a0\u00bbtext_text_shadow_style,%91object Object%93″ link_text_shadow_horizontal_length=\u00a0\u00bblink_text_shadow_style,%91object Object%93″ link_text_shadow_vertical_length=\u00a0\u00bblink_text_shadow_style,%91object Object%93″ link_text_shadow_blur_strength=\u00a0\u00bblink_text_shadow_style,%91object Object%93″ ul_text_shadow_horizontal_length=\u00a0\u00bbul_text_shadow_style,%91object Object%93″ ul_text_shadow_vertical_length=\u00a0\u00bbul_text_shadow_style,%91object Object%93″ ul_text_shadow_blur_strength=\u00a0\u00bbul_text_shadow_style,%91object Object%93″ ol_text_shadow_horizontal_length=\u00a0\u00bbol_text_shadow_style,%91object Object%93″ ol_text_shadow_vertical_length=\u00a0\u00bbol_text_shadow_style,%91object Object%93″ ol_text_shadow_blur_strength=\u00a0\u00bbol_text_shadow_style,%91object Object%93″ quote_text_shadow_horizontal_length=\u00a0\u00bbquote_text_shadow_style,%91object Object%93″ quote_text_shadow_vertical_length=\u00a0\u00bbquote_text_shadow_style,%91object Object%93″ quote_text_shadow_blur_strength=\u00a0\u00bbquote_text_shadow_style,%91object Object%93″ header_text_shadow_horizontal_length=\u00a0\u00bbheader_text_shadow_style,%91object Object%93″ header_text_shadow_vertical_length=\u00a0\u00bbheader_text_shadow_style,%91object Object%93″ header_text_shadow_blur_strength=\u00a0\u00bbheader_text_shadow_style,%91object Object%93″ header_2_text_shadow_horizontal_length=\u00a0\u00bbheader_2_text_shadow_style,%91object Object%93″ header_2_text_shadow_vertical_length=\u00a0\u00bbheader_2_text_shadow_style,%91object Object%93″ header_2_text_shadow_blur_strength=\u00a0\u00bbheader_2_text_shadow_style,%91object Object%93″ header_3_text_shadow_horizontal_length=\u00a0\u00bbheader_3_text_shadow_style,%91object Object%93″ header_3_text_shadow_vertical_length=\u00a0\u00bbheader_3_text_shadow_style,%91object Object%93″ header_3_text_shadow_blur_strength=\u00a0\u00bbheader_3_text_shadow_style,%91object Object%93″ header_4_text_shadow_horizontal_length=\u00a0\u00bbheader_4_text_shadow_style,%91object Object%93″ header_4_text_shadow_vertical_length=\u00a0\u00bbheader_4_text_shadow_style,%91object Object%93″ header_4_text_shadow_blur_strength=\u00a0\u00bbheader_4_text_shadow_style,%91object Object%93″ header_5_text_shadow_horizontal_length=\u00a0\u00bbheader_5_text_shadow_style,%91object Object%93″ header_5_text_shadow_vertical_length=\u00a0\u00bbheader_5_text_shadow_style,%91object Object%93″ header_5_text_shadow_blur_strength=\u00a0\u00bbheader_5_text_shadow_style,%91object Object%93″ header_6_text_shadow_horizontal_length=\u00a0\u00bbheader_6_text_shadow_style,%91object Object%93″ header_6_text_shadow_vertical_length=\u00a0\u00bbheader_6_text_shadow_style,%91object Object%93″ header_6_text_shadow_blur_strength=\u00a0\u00bbheader_6_text_shadow_style,%91object Object%93″ z_index_tablet=\u00a0\u00bb500″]<\/p>\n

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Homeostasis is seen as the optimal functioning condition for a living unit, in which a steady state is reached with a certain constancy of the immediate environment. This steady state is, however, persistently challenged by internal or external changes in the environment. Most changes can be considered as potentially harmful and detrimental, and we will tackle the response mechanisms that safeguard the steady state in \u201cadversary\u201d conditions.<\/div>\n<\/div>\n<\/div>\n

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Heart-shaped empty testicular tubule<\/h4>\n

DAPI staining of testicular tubules from a mouse model of male infertility.<\/p><\/div>\n<\/div>\n<\/div>\n

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\u00a9 Julie COCQUET, Institut Cochin<\/div>\n<\/div>\n<\/div>\n

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Stress challenges<\/h3>\n

Most frequent among those challenges, DNA lesions are handled by a complex machinery that ensures correct repair of the nucleic acid molecules. However, beyond genome stability, a key question that we tackle is how the integrity of the epigenome is preserved during DNA damage and repair<\/strong>, and whether the mechanisms and players involved differ according to chromatin context (euchromatin versus heterochromatin) and nuclear organization (compartments). We also explore the consequences of environmental insult at the level of a whole organism<\/strong>, by digging into the interesting concept of epigenetic scars induced by prenatal stress, notably in the context of brain development. Novel mechanisms that explain how stress-responses triggered by prenatal stress protect or alter the epigenome are being deciphered, unravelling both the robustness and vulnerability of the epigenetic layer of information.
Cells and organisms are submitted to unforeseen stressors of external (environmental toxins, drugs) or internal (secreted misfolded cellular proteins) nature. These stressors can challenge cellular integrity by impacting directly on the stability of the DNA and the epigenome or by impairing the function of cell surface receptors important for cellular homeostasis. We study the consequences of internal stressors like amyloid \u03b2 peptides and the Tau proteins<\/strong> that are secreted as misfolded proteins in the course of neurodegenerative diseases and that have devasting effects on cellular integrity and memory formation. The impact on cellular functions is our primary focus.
From a philosophical viewpoint, identity maintenance and stress response have been conceived in the general framework of robustness.<\/strong> For evolutionary reasons, living systems are robust, both regarding environmental alterations and genetic mutations. This robustness of living systems concerns the functioning of organisms, including stress response, and their development, which involves the concept of canalization as robustness regarding genetic mutations. Response to stress is thus included within a multilayered hierarchical property of organism robustness, which raises two evolutionary issues, namely the causes of its evolution, and its role within evolution. Hence, a future challenge is to situate the Labex\u2019s findings on stress response within a general theory of robustness that would take into account its hierarchical structure and its dual evolutionary meaning.<\/div>\n

Mechanical cues and signaling<\/h3>\n

Control of cell and tissue identity has long been shown to be triggered by morphogens and downstream signaling pathway. However, recent accumulating experimental evidence led to the recognition that mechanical properties of tissues can control a variety of cell functions including cell stemness, cell proliferation and cell death. Physical properties of the tissue environment appear as a key regulator of its maintenance and integrity. Along this line, we focus on the impact of mechanosensing and mechanotransduction pathways on cell assemblies. This may rely on properties emerging at the multicellular level, associated to the physical properties of the environment, the position of the cells relative to each other and to the coexistence and complex interaction of multiple cell types over space and time. Adult epithelia, for example, are in a constant dynamic equilibrium of cell proliferation, migration, differentiation and cell death. Such homeostasis process is highly important as it is the key of functional tissue renewal and it maintains the epithelial integrity. A revolutionary breakthrough in the development of organoids in vitro from isolated adult stem cells has been achieved in the past decade. As another example, the development of the skeletal muscle cells implicates a tight coordination of adhesion, contraction and interaction with their environment. In the case of motile and contractile cells such as muscle cells, the coupling to various (i.e. soft or stiff) substrates can control the fusion processes and thus muscle formation and repair.
In this context, forces, cell-cell interactions and physical changes in micro-environments may modulate the transduction of mechanical signals across the cell membrane and hence modify the fusogenic properties of primary myoblasts and myofibers. The rapid development of micro\/nano-engineering techniques and functional biomaterials have empowered biologists and bioengineers to precisely control aspects of the in vitro cell microenvironments. How cues from tissue geometries and environment mechanical properties may control the maintenance of stemness and cellular identities remains a puzzling issue to understand tissue homeostasis. These include to understand how the dynamics and organization of multicellular systems, as well as how stem cell proliferation and differentiation impact self-renewal equilibrium, and ultimately cell proliferation, death and extrusion. Here, we focus on physical cellular sensing perceived by cell-cell adhesion complexes that can propagate over multiple cells. It then leads to an internal rearrangement at the inner cell membrane together with active forces exerted by the actomyosin cytoskeleton that propagate from the cytoplasm to the nucleus but also. Recent studies have shown that various transcription factors including YAP, \u03b2-catenin can shuttle between the cytoplasm and the nucleus in response to mechanosensing in cellular monolayers. We study the interplay between mechanical constrains and molecular mechanisms implicating chromatin dynamics, gene localization and expression and nuclear transport across nuclear pores to understand tissue-scale homeostasis.<\/strong> The perception of mechanical signals from molecular to multicellular scales over various time-scales have strong implications to define single-cell identity within a population.<\/div>\n<\/div>\n

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\u00c0<\/span> lire aussi<\/h2>\n

[\/et_pb_text][et_pb_blog _builder_version=\u00a0\u00bb3.21″ posts_number=\u00a0\u00bb4″ include_categories=\u00a0\u00bb13″ show_author=\u00a0\u00bboff\u00a0\u00bb show_date=\u00a0\u00bboff\u00a0\u00bb show_pagination=\u00a0\u00bboff\u00a0\u00bb border_width_bottom_fullwidth=\u00a0\u00bb1px\u00a0\u00bb border_color_bottom_fullwidth=\u00a0\u00bbrgba(51,51,51,0.18)\u00a0\u00bb custom_padding=\u00a0\u00bb||50px|\u00a0\u00bb module_id=\u00a0\u00bbpage_type_blog\u00a0\u00bb header_level=\u00a0\u00bbh4″ \/][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"

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Homeostasis is seen as the optimal functioning condition for a living unit, in which a steady state is reached with a certain constancy of the immediate environment. This steady state is, however, persistently challenged by internal or external changes in the environment. Most changes can be considered as potentially harmful and detrimental, and we… Lire la suite Integrity in response to stress and challenge<\/span><\/a><\/p>\n","protected":false},"author":236,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"

[et_pb_section bb_built=\"1\" next_background_color=\"#000000\" inner_width=\"auto\" inner_max_width=\"none\"][et_pb_row][et_pb_column type=\"4_4\"][et_pb_post_title admin_label=\"Titre de la page\" _builder_version=\"3.22.1\" meta=\"off\" featured_image=\"off\" \/][\/et_pb_column][\/et_pb_row][et_pb_row][et_pb_column type=\"3_4\"][et_pb_text admin_label=\"Intro\" _builder_version=\"3.22.1\" module_id=\"intro\" text_text_shadow_horizontal_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_vertical_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_blur_strength=\"text_text_shadow_style,%91object Object%93\" link_text_shadow_horizontal_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_vertical_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_blur_strength=\"link_text_shadow_style,%91object Object%93\" ul_text_shadow_horizontal_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_vertical_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_blur_strength=\"ul_text_shadow_style,%91object Object%93\" ol_text_shadow_horizontal_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_vertical_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_blur_strength=\"ol_text_shadow_style,%91object Object%93\" quote_text_shadow_horizontal_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_vertical_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_blur_strength=\"quote_text_shadow_style,%91object Object%93\" header_text_shadow_horizontal_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_vertical_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_blur_strength=\"header_text_shadow_style,%91object Object%93\" header_2_text_shadow_horizontal_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_vertical_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_blur_strength=\"header_2_text_shadow_style,%91object Object%93\" header_3_text_shadow_horizontal_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_vertical_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_blur_strength=\"header_3_text_shadow_style,%91object Object%93\" header_4_text_shadow_horizontal_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_vertical_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_blur_strength=\"header_4_text_shadow_style,%91object Object%93\" header_5_text_shadow_horizontal_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_vertical_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_blur_strength=\"header_5_text_shadow_style,%91object Object%93\" header_6_text_shadow_horizontal_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_vertical_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_blur_strength=\"header_6_text_shadow_style,%91object Object%93\" z_index_tablet=\"500\"]<\/p>

L'hom\u00e9ostasie est consid\u00e9r\u00e9e comme la condition de fonctionnement optimale pour tout \u00e9l\u00e9ment vivant, dans laquelle un \u00e9tat stationnaire est atteint avec une certaine constance de l'environnement imm\u00e9diat. Cet \u00e9tat stationnaire est cependant constamment remis en question par des changements internes ou externes de l'environnement. La plupart des changements peuvent \u00eatre consid\u00e9r\u00e9s comme potentiellement nocifs et pr\u00e9judiciables. Nous nous int\u00e9ressons en particulier aux m\u00e9canismes de r\u00e9ponse qui pr\u00e9servent l'\u00e9tat d'\u00e9quilibre dans des conditions \u00abadverses\u00bb.<\/p><\/div><\/div><\/div>

[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_4\"][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=\"3.19.11\" module_id=\"image-page-type\" width=\"80%\" max_width=\"1080px\"][et_pb_column type=\"3_4\"][et_pb_image admin_label=\"Image 1920 x 1080\" _builder_version=\"3.22.1\" src=\"https:\/\/wordpress-test.app.u-pariscite.fr\/who-am-i\/wp-content\/uploads\/sites\/15\/2021\/07\/00037_01_empty-tubule_1920.jpg\" module_id=\"image-page\" z_index_tablet=\"500\" \/][\/et_pb_column][et_pb_column type=\"1_4\"][et_pb_text admin_label=\"Texte image\" _builder_version=\"3.22.1\" module_id=\"texte-image\" custom_margin=\"|-15px||\" text_text_shadow_horizontal_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_vertical_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_blur_strength=\"text_text_shadow_style,%91object Object%93\" link_text_shadow_horizontal_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_vertical_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_blur_strength=\"link_text_shadow_style,%91object Object%93\" ul_text_shadow_horizontal_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_vertical_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_blur_strength=\"ul_text_shadow_style,%91object Object%93\" ol_text_shadow_horizontal_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_vertical_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_blur_strength=\"ol_text_shadow_style,%91object Object%93\" quote_text_shadow_horizontal_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_vertical_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_blur_strength=\"quote_text_shadow_style,%91object Object%93\" header_text_shadow_horizontal_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_vertical_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_blur_strength=\"header_text_shadow_style,%91object Object%93\" header_2_text_shadow_horizontal_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_vertical_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_blur_strength=\"header_2_text_shadow_style,%91object Object%93\" header_3_text_shadow_horizontal_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_vertical_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_blur_strength=\"header_3_text_shadow_style,%91object Object%93\" header_4_text_shadow_horizontal_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_vertical_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_blur_strength=\"header_4_text_shadow_style,%91object Object%93\" header_5_text_shadow_horizontal_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_vertical_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_blur_strength=\"header_5_text_shadow_style,%91object Object%93\" header_6_text_shadow_horizontal_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_vertical_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_blur_strength=\"header_6_text_shadow_style,%91object Object%93\" z_index_tablet=\"500\"]<\/p>

Tubule testiculaire vide en forme de c\u0153ur<\/h4>

Marquage DAPI d'un tubule testiculaire d'un mod\u00e8le murin d'infertilit\u00e9 masculine.<\/p><\/div><\/div><\/div>

[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row][et_pb_column type=\"4_4\"][et_pb_text admin_label=\"l\u00e9gende\" _builder_version=\"3.22.1\" module_id=\"legende\" text_text_shadow_horizontal_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_vertical_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_blur_strength=\"text_text_shadow_style,%91object Object%93\" link_text_shadow_horizontal_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_vertical_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_blur_strength=\"link_text_shadow_style,%91object Object%93\" ul_text_shadow_horizontal_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_vertical_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_blur_strength=\"ul_text_shadow_style,%91object Object%93\" ol_text_shadow_horizontal_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_vertical_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_blur_strength=\"ol_text_shadow_style,%91object Object%93\" quote_text_shadow_horizontal_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_vertical_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_blur_strength=\"quote_text_shadow_style,%91object Object%93\" header_text_shadow_horizontal_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_vertical_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_blur_strength=\"header_text_shadow_style,%91object Object%93\" header_2_text_shadow_horizontal_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_vertical_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_blur_strength=\"header_2_text_shadow_style,%91object Object%93\" header_3_text_shadow_horizontal_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_vertical_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_blur_strength=\"header_3_text_shadow_style,%91object Object%93\" header_4_text_shadow_horizontal_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_vertical_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_blur_strength=\"header_4_text_shadow_style,%91object Object%93\" header_5_text_shadow_horizontal_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_vertical_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_blur_strength=\"header_5_text_shadow_style,%91object Object%93\" header_6_text_shadow_horizontal_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_vertical_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_blur_strength=\"header_6_text_shadow_style,%91object Object%93\" z_index_tablet=\"500\"]<\/p>

\u00a9 Julie COCQUET, Institut Cochin<\/p><\/div><\/div><\/div>

[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row][et_pb_column type=\"3_4\"][et_pb_text _builder_version=\"3.22.1\" module_id=\"contenu\" text_text_shadow_horizontal_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_vertical_length=\"text_text_shadow_style,%91object Object%93\" text_text_shadow_blur_strength=\"text_text_shadow_style,%91object Object%93\" link_text_shadow_horizontal_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_vertical_length=\"link_text_shadow_style,%91object Object%93\" link_text_shadow_blur_strength=\"link_text_shadow_style,%91object Object%93\" ul_text_shadow_horizontal_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_vertical_length=\"ul_text_shadow_style,%91object Object%93\" ul_text_shadow_blur_strength=\"ul_text_shadow_style,%91object Object%93\" ol_text_shadow_horizontal_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_vertical_length=\"ol_text_shadow_style,%91object Object%93\" ol_text_shadow_blur_strength=\"ol_text_shadow_style,%91object Object%93\" quote_text_shadow_horizontal_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_vertical_length=\"quote_text_shadow_style,%91object Object%93\" quote_text_shadow_blur_strength=\"quote_text_shadow_style,%91object Object%93\" header_text_shadow_horizontal_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_vertical_length=\"header_text_shadow_style,%91object Object%93\" header_text_shadow_blur_strength=\"header_text_shadow_style,%91object Object%93\" header_2_text_shadow_horizontal_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_vertical_length=\"header_2_text_shadow_style,%91object Object%93\" header_2_text_shadow_blur_strength=\"header_2_text_shadow_style,%91object Object%93\" header_3_text_shadow_horizontal_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_vertical_length=\"header_3_text_shadow_style,%91object Object%93\" header_3_text_shadow_blur_strength=\"header_3_text_shadow_style,%91object Object%93\" header_4_text_shadow_horizontal_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_vertical_length=\"header_4_text_shadow_style,%91object Object%93\" header_4_text_shadow_blur_strength=\"header_4_text_shadow_style,%91object Object%93\" header_5_text_shadow_horizontal_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_vertical_length=\"header_5_text_shadow_style,%91object Object%93\" header_5_text_shadow_blur_strength=\"header_5_text_shadow_style,%91object Object%93\" header_6_text_shadow_horizontal_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_vertical_length=\"header_6_text_shadow_style,%91object Object%93\" header_6_text_shadow_blur_strength=\"header_6_text_shadow_style,%91object Object%93\" z_index_tablet=\"500\"]<\/p>

Challenges de r\u00e9sistance au stress<\/h3>

Le plus fr\u00e9quent de ces challenges consiste en des l\u00e9sions de l'ADN, trait\u00e9es ensuite par une machinerie complexe assurant une r\u00e9paration correcte des mol\u00e9cules d'acide nucl\u00e9ique. Cependant, au-del\u00e0 de la stabilit\u00e9 du g\u00e9nome, une question cl\u00e9 que nous abordons est de savoir comment l'int\u00e9grit\u00e9 de l'\u00e9pig\u00e9nome est pr\u00e9serv\u00e9e pendant les dommages et la r\u00e9paration de l'ADN<\/strong>, et si les m\u00e9canismes et les acteurs impliqu\u00e9s diff\u00e8rent selon le contexte de la chromatine (euchromatine versus h\u00e9t\u00e9rochromatine) et l'organisation nucl\u00e9aire (compartiments). Nous explorons \u00e9galement les cons\u00e9quences des atteintes \u00e0 l'environnement au niveau de tout un organisme<\/strong>, en approfondissant le concept de cicatrices \u00e9pig\u00e9n\u00e9tiques induites par le stress pr\u00e9natal, notamment dans le cadre du d\u00e9veloppement c\u00e9r\u00e9bral. De nouveaux m\u00e9canismes qui expliquent comment les r\u00e9ponses au stress d\u00e9clench\u00e9es par le stress pr\u00e9natal prot\u00e8gent ou alt\u00e8rent l'\u00e9pig\u00e9nome sont \u00e9tudi\u00e9s, r\u00e9v\u00e9lant \u00e0 la fois la robustesse et la vuln\u00e9rabilit\u00e9 de la couche \u00e9pig\u00e9n\u00e9tique d'information.
Les cellules et les organismes sont soumis \u00e0 des facteurs de stress impr\u00e9vus de nature externe (toxines environnementales, m\u00e9dicaments) ou interne (prot\u00e9ines cellulaires mal repli\u00e9es s\u00e9cr\u00e9t\u00e9es). Ces facteurs de stress peuvent remettre en cause l'int\u00e9grit\u00e9 cellulaire en ayant un impact direct sur la stabilit\u00e9 de l'ADN et de l'\u00e9pig\u00e9nome ou en alt\u00e9rant la fonction des r\u00e9cepteurs de surface cellulaire importants pour l'hom\u00e9ostasie cellulaire. Nous \u00e9tudions les cons\u00e9quences de facteurs de stress internes comme les peptides amylo\u00efdes \u03b2 et les prot\u00e9ines Tau<\/strong> qui sont s\u00e9cr\u00e9t\u00e9es sous forme de prot\u00e9ines mal repli\u00e9es au cours de maladies neurod\u00e9g\u00e9n\u00e9ratives et qui ont des effets d\u00e9vastateurs sur l'int\u00e9grit\u00e9 cellulaire et la formation de la m\u00e9moire. L'impact sur les fonctions cellulaires sera notre objectif principal.
D'un point de vue philosophique, le maintien de l'identit\u00e9 et la r\u00e9ponse au stress ont \u00e9t\u00e9 con\u00e7us \u00e0 travers la notion de robustesse.<\/strong> Pour des raisons \u00e9volutives, les syst\u00e8mes vivants sont robustes, \u00e0 la fois en ce qui concerne les alt\u00e9rations environnementales et les mutations g\u00e9n\u00e9tiques. Cette robustesse des syst\u00e8mes vivants concerne le fonctionnement des organismes, y compris la r\u00e9ponse au stress, et leur d\u00e9veloppement, ce qui implique le concept de canalisation, c'est \u00e0 dire la robustesse vis-\u00e0-vis des mutations g\u00e9n\u00e9tiques. La r\u00e9ponse au stress est ainsi inclue dans une propri\u00e9t\u00e9 hi\u00e9rarchique multicouche de la robustesse de l'organisme, ce qui soul\u00e8ve deux questions \u00e9volutives, \u00e0 savoir les causes de son \u00e9volution et son r\u00f4le dans l'\u00e9volution. Par cons\u00e9quent, notre d\u00e9fi est d'inclure les r\u00e9sultats sur la r\u00e9ponse au stress dans une th\u00e9orie g\u00e9n\u00e9rale de la robustesse qui prendrait en compte sa structure hi\u00e9rarchique et sa double signification \u00e9volutive.<\/p>

\u00a0<\/p><\/div>

Signaux m\u00e9caniques et signalisation<\/h3>

Il a \u00e9t\u00e9 d\u00e9montr\u00e9 depuis longtemps que le contr\u00f4le de l'identit\u00e9 des cellules et des tissus est d\u00e9clench\u00e9 par les morphog\u00e8nes et la voie de signalisation en aval. Cependant, l'accumulation de preuves exp\u00e9rimentales r\u00e9centes a conduit \u00e0 la reconnaissance que les propri\u00e9t\u00e9s m\u00e9caniques des tissus peuvent contr\u00f4ler une vari\u00e9t\u00e9 de fonctions cellulaires, y compris le caract\u00e8re \"souche\", la prolif\u00e9ration cellulaire et la mort cellulaire. Les propri\u00e9t\u00e9s physiques de l'environnement tissulaire apparaissent comme un r\u00e9gulateur cl\u00e9 de son maintien et de son int\u00e9grit\u00e9. Dans cette optique, nous nous concentrons sur l'impact des voies de m\u00e9cano-d\u00e9tection et de m\u00e9cano-transduction sur les assemblages cellulaires. Cela peut s'appuyer sur des propri\u00e9t\u00e9s \u00e9mergeant au niveau multicellulaire, associ\u00e9es aux propri\u00e9t\u00e9s physiques de l'environnement, \u00e0 la position des cellules les unes par rapport aux autres et \u00e0 la coexistence et \u00e0 l'interaction complexe de plusieurs types de cellules dans l'espace et le temps. Les \u00e9pith\u00e9liums adultes, par exemple, sont dans un \u00e9quilibre dynamique constant de prolif\u00e9ration cellulaire, de migration, de diff\u00e9renciation et de mort cellulaire. Un tel processus d'hom\u00e9ostasie est tr\u00e8s important car il est la cl\u00e9 du renouvellement fonctionnel des tissus et il maintient l'int\u00e9grit\u00e9 \u00e9pith\u00e9liale. Une perc\u00e9e r\u00e9volutionnaire dans le d\u00e9veloppement d'organo\u00efdes in vitro<\/em> \u00e0 partir de cellules souches adultes isol\u00e9es a \u00e9t\u00e9 r\u00e9alis\u00e9e dans la derni\u00e8re d\u00e9cennie. Comme autre exemple, le d\u00e9veloppement des cellules musculaires squelettiques implique une coordination \u00e9troite d'adh\u00e9sion, de contraction et d'interaction avec leur environnement. Dans le cas de cellules mobiles et contractiles telles que les cellules musculaires, le couplage \u00e0 divers substrats (c'est-\u00e0-dire mous ou rigides) peut contr\u00f4ler les processus de fusion et donc la formation et la r\u00e9paration musculaires.<\/p>

Dans ce contexte, les forces, les interactions cellule-cellule et les changements physiques dans les micro-environnements peuvent moduler la transduction des signaux m\u00e9caniques \u00e0 travers la membrane cellulaire et donc modifier les propri\u00e9t\u00e9s fusog\u00e8nes des myoblastes primaires et des myofibres. Le d\u00e9veloppement rapide des techniques de micro \/ nano-ing\u00e9nierie et des biomat\u00e9riaux fonctionnels a permis aux biologistes et aux bio-ing\u00e9nieurs de contr\u00f4ler avec pr\u00e9cision les aspects des micro-environnements cellulaires in vitro<\/em>. Comment les indices des g\u00e9om\u00e9tries tissulaires et des propri\u00e9t\u00e9s m\u00e9caniques de l'environnement peuvent contr\u00f4ler le maintien de la tige et des identit\u00e9s cellulaires reste un probl\u00e8me pour comprendre l'hom\u00e9ostasie tissulaire. Il s'agit notamment de comprendre comment la dynamique et l'organisation des syst\u00e8mes multicellulaires, ainsi que comment la prolif\u00e9ration et la diff\u00e9renciation des cellules souches ont un impact sur l'\u00e9quilibre d'auto-renouvellement, et finalement sur la prolif\u00e9ration, la mort et l'extrusion des cellules. Nous nous concentrons sur la d\u00e9tection physique per\u00e7ue par les complexes d'adh\u00e9sion cellule-cellule qui peuvent se propager sur plusieurs cellules. Elle conduit \u00e0 un r\u00e9arrangement interne au niveau de la membrane cellulaire interne en m\u00eame temps que des forces actives exerc\u00e9es par le cytosquelette d'actomyosine se propagent du cytoplasme au noyau. Des \u00e9tudes r\u00e9centes ont montr\u00e9 que divers facteurs de transcription, y compris YAP\/\u03b2-cat\u00e9nine, peuvent faire la navette entre le cytoplasme et le noyau en r\u00e9ponse \u00e0 la m\u00e9cano-d\u00e9tection dans les monocouches cellulaires. Nous \u00e9tudions l'interaction entre les contraintes m\u00e9caniques et les m\u00e9canismes mol\u00e9culaires impliquant la dynamique de la chromatine, la localisation et l'expression des g\u00e8nes et le transport nucl\u00e9aire \u00e0 travers les pores nucl\u00e9aires pour comprendre l'hom\u00e9ostasie \u00e0 l'\u00e9chelle des tissus.<\/strong> La perception des signaux m\u00e9caniques, des \u00e9chelles mol\u00e9culaires aux \u00e9chelles multicellulaires et \u00e0 diff\u00e9rentes \u00e9chelles de temps, aura de fortes implications pour d\u00e9finir l'identit\u00e9 unicellulaire au sein d'une population.<\/p><\/div><\/div>

[\/et_pb_text][\/et_pb_column][et_pb_column type=\"1_4\"][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section bb_built=\"1\" specialty=\"off\" _builder_version=\"3.21\" custom_padding=\"0px||0px|\" prev_background_color=\"#000000\" inner_width=\"auto\" inner_max_width=\"none\"][et_pb_row _builder_version=\"3.19.11\" width=\"80%\" max_width=\"1080px\"][et_pb_column type=\"4_4\"][et_pb_text admin_label=\"\u00c0 lire aussi\" _builder_version=\"3.21\"]<\/p>

\u00c0<\/span> lire aussi<\/h2>

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