报告题目：Fate Specification and Self-Renewal of Skin Stem Cells

报告人：  陈婷博士  Rockefeller University

主持人：  王传贵 教授

时  间：  6月11日 13:30―15:00（周一）

地  点：  闵行生命科学学院大楼469会议室

报告人简介：陈婷博士，Rockefeller University，近年来主要围绕干细胞生物学领域前沿的关键问题开展研究，先后在Nature （2012）， Cell Stem Cell （2009），Nature Cell Biology （2007）发表第一作者研究论文。

报告内容简介：Adult stem cells (SCs) sustain tissue maintenance and regeneration throughout the lifetime of an animal. They often reside in specific signaling niches that orchestrate the stem cell’s balancing act between quiescence and cell cycle re-entry based upon demand for tissue regeneration.  How SCs maintain their capacity to replenish themselves following tissue regeneration is still poorly understood. Here, we use RNA interference (RNAi)-based loss-of-function screening as a powerful approach to uncover transcriptional regulators governing SC self-renewal and regenerative potential. Hair follicle (HF) SCs provide an ideal paradigm. They’ve been purified and characterized from their native niche in vivo, and in contrast to their rapidly dividing progeny, they can be maintained and passaged long-term in vitro. Focusing on nuclear proteins/transcription factors enriched in SCs versus progenies, we screened ~2,000 shRNAs for their impact on long-term but not short-term self-renewal in vitro. To address the physiological relevance of our findings, we selected one candidate, Tbx1, surfacing in the screen. Expressed in many tissues, this transcription factor has not been studied in the context of SC biology. By conditionally ablating Tbx1 in vivo, we show that tissue regeneration during homeostasis occurs normally but is dramatically delayed. Devising an in vivo assay for SC replenishment, we then show that when challenged with repetitive bouts of regeneration, the Tbx1-deficient SC niche becomes progressively depleted.  Addressing mechanism, we discover that Tbx1 acts as an intrinsic rheostat of BMP signalling, the gatekeeper governing the transition between SC quiescence and proliferation in HFs. Our results validate the RNAi screen and underscore its power in unearthing new players governing SC self-renewal and tissue-regenerative potential.