Abstract: Series 103, Lecture 4

The Harvey Lectures Series 103 (2007—2008)

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Lecture #4: Thursday, February 21, 2008 — Time and Location

Stem Cell Regulation in vivo Within Tissue Niches

Allan C Spradling, PhD

Allan C Spradling, PhD

Director, Department of Embryology, Carnegie Institution
Investigator, Howard Hughes Medical Institute

Howard Hughes Medical Institute, Johns Hopkins University

Baltimore, Maryland

Dr Spradling's Website

Adult stem cells mediate tissue repair and replenishment within organisms spanning a broad phylogenetic range from Planaria to humans. Drosophila genetic technology allows these rare cells to be identified and analyzed with single-cell and single-gene resolution. Marking tissue stem cells and their immature (transit-amplifying) progeny using inducible lineage tracers reveals that both germline and somatic gonadal stem cells are maintained within distinct tissue niches. Niche-bound stem cells compete with the daughters of other stem cells for continued niche occupancy, a process that may mitigate the effects of somatic mutations. Other stem cells, such as multipotent intestinal stem cells, program their daughters to become enterocytes or enteroendocrine cells by sending a strong or weak Notch signal, respectively. How stem cells remain undifferentiated within the niche, and how their daughters initiate diffferentiation and revert back to the stem cell state under appropriate conditions remain central questions. The ubiquitin-specific protease Scrawny appears to play a common role, as it is needed to maintain at least four different types of stem cell. Scrawny contributes to gene silencing in vivo and recombinant Scrawny deubiquitylates Histone H2B in vitro, suggesting a prominent role for chromatin-mediated gene repression.