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!