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Defining the cellular dynamics leading to tissue expansion (EXPAND)
Start date: Jun 1, 2014, End date: May 31, 2019 PROJECT  FINISHED 

Stem cells (SCs) ensure the development of the different tissues during morphogenesis, their physiological turnover during adult life and tissue repair after injuries. .Our lab has recently developed new methods to study by lineage tracing the cellular hierarchy that sustains homeostasis and repair of the epidermis and to identify distinct populations of SCs and progenitors ensuring mammary gland and prostate postnatal development.While quantitative clonal analysis combined with mathematical modeling has been used recently to decipher the cellular basis of tissue homeostasis, such experimental approaches have never been used so far in mammals to investigate the cellular hierarchy acting during tissue expansion such as postnatal development and tissue repair.In this project, we will use a multi-disciplinary approach combining mouse genetic lineage tracing and clonal analysis, mathematical modeling, proliferation kinetics, transcriptional profiling, and functional experiments to investigate the cellular and molecular mechanisms regulating tissue expansion during epithelial development and tissue repair and how the fate of these cells is controlled during this process.1. We will define the clonal and proliferation dynamics of tissue expansion in the epidermis, the mammary gland and the prostate during postnatal growth and adult tissue regeneration.2. We will define the clonal and proliferation dynamics of tissue expansion in the adult epidermis following wounding and mechanical force mediated tissue expansion.3. We will define the mechanisms that regulate the switch from multipotent to unipotent cell fate during development of glandular epithelia.Defining the cellular and molecular mechanisms underlying tissue growth and expansion during development and how these mechanisms differ from tissue regeneration in adult may have important implications for understanding the causes of certain developmental defects and for regenerative medicine.
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