Seminar
Topic: Fate Specication and Self-Renewal of Skin Stem Cells
Speaker: Ting Chen, Laboratory of Mammalian Cell, Biology and Development, Rockefeller University
Time: 06/19/2012, 16:30
Venue: New Biology Building, 143
Abstract:
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.
Please refer to the attached poster and CV of Dr. Chen's for more information.
Thank you for your attention!
