Genetic and Epigenetic Regulation of Stem Cell Fat.. (StemDNAFate)
Genetic and Epigenetic Regulation of Stem Cell Fate
Start date: Apr 1, 2013,
End date: Mar 31, 2018
Stem cells play crucial roles in establishing and repairing tissues, yet our knowledge of their properties, how they assure organogenesis and effect regeneration in distinct physiological contexts remains limited. A major challenge in stem cell biology is investigating these cells in their natural state in vivo, and obtaining highly pure and sufficient quantities for characterisation.Skeletal myogenesis provides an excellent paradigm to investigate stem cell function and regenerative biology because of its accessibility, and its striking ability to regenerate efficiently. Futhermore, the same individual can undergo multiple rounds of muscle injury thereby permitting the long term study of stem cell turnover and homeostasis after inflicted trauma without life threatening consequences or complex surgical procedures.The objective of this research programme is to identify mouse stem cell properties and understand how they regulate cell fate choice in different contexts by modulating their modes of cell divisions. Specifically, biased DNA segregation, which has been reported in diverse organisms from bacteria to vertebrates and is thus an evolutionary ancient phenomenon, will be investigated. Notably, we developed genetic tools that allow us to isolate prospectively those cells that execute asymmetric vs. symmetric cell divisions during regeneration, and directly linked cell fates with biased DNA segregation. The use of innovative nucleotides, micropatterns to mimic the niche, epigenetic, genetic and single cell transcriptomics strategies comprise a multi-pronged strategy to uncover the underlying mechanisms that govern asymmetric cell fates and biased DNA segregation. This knowledge will be projected to tissuegenesis using complementary clonal lineage tracing and live imaging of cell divisions in vivo. These studies aim to identify the diverse modes of stem cell divisions during tissuegenesis, information that can significantly impact on regenerative medicine.
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