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Mechanisms of epidermal stratification and force-mediated regulation of stem cell fate and positioning

Project description

How tissue geometry and cell shape guide stem cell fate and positioning

Epidermal stem cells (ESC) commit to differentiate and delaminate from the basal layer to form suprabasal layers while achieving the dynamic turnover and maintenance of the skin barrier function. Cells within the epidermis are constantly exposed to tissue- and cell-scale forces that change cell and nuclear shape and volume. The EU-funded SkinForce project is testing the hypothesis that dynamic cell and nuclear shape changes play a central role in regulating ESC fate and in coupling these changes to cell positioning within the tissue. The research will combine innovative live embryo imaging, quantitative image analysis and a transgenic reporter mice model to decipher the dynamics of epidermal morphogenesis.

Objective

As a self-renewing organ maintained by multiple distinct stem cell populations, the epidermis represents an outstanding, clinically relevant research paradigm to address mechanisms of stem cell regulation. To achieve the dynamic turnover and maintenance of the critical skin barrier function, epidermal stem cells (SC) commit to differentiate and delaminate from the basal layer to form suprabasal layers. What triggers SC differentiation, how the differentiating cells move upwards, and how differentiation and self-renewing divisions are balanced remain key open questions. Cells within the epidermis are constantly exposed to tissue- and cell-scale forces that result in changes in cell and nuclear shape and volume. Based on the emerging role of cell density and size in regulating SC fate, I hypothesize that dynamic nuclear and cell shape changes play central roles in regulating epidermal SC fate and in coupling fate changes to cell positioning within the tissue. By combining an innovative, live embryo imaging pipeline, quantitative image analysis, and theoretical models, I aim to decipher the dynamics of epidermal morphogenesis. Using transgenic reporter mice for the nucleus, plasma membrane, cytoskeleton, and differentiation, I will map large-scale and local mechanical transitions along the developmental timeline and correlate them with nuclear and cell shape changes, cell division, differentiation and delamination. I will combine these quantitative imaging experiments with computational modeling, genetic manipulation of contractility, spatial single cell transcriptomics and in vitro cell biology to discover the cellular and molecular mechanism by which tissue geometry and cell/nuclear shape guide cell fate and dynamic positioning. Altogether, this project will uncover fundamental mechanisms of epidermal stratification during development and homeostasis.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 58 338,96
Address
HOFGARTENSTRASSE 8
80539 Munchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 58 338,96

Participants (1)

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