WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation

Cell
Tamara OuspenskaiaElaine Fuchs

Abstract

Adult stem cell (SC) maintenance and differentiation are known to depend on signals received from the niche. Here, however, we demonstrate a mechanism for SC specification and regulation that is niche independent. Using immunofluorescence, live imaging, genetics, cell-cycle analyses, in utero lentiviral transduction, and lineage-tracing, we show that in developing hair buds, SCs are born from asymmetric divisions that differentially display WNT and SHH signaling. Displaced WNT(lo) suprabasal daughters become SCs that respond to paracrine SHH and symmetrically expand. By contrast, basal daughters remain WNT(hi). They express but do not respond to SHH and hence maintain slow-cycling, asymmetric divisions. Over time, they become short-lived progenitors, generating differentiating daughters rather than SCs. Thus, in contrast to an established niche that harbors a fixed SC pool whose expelled progeny differentiate, asymmetric divisions first specify and displace early SCs into an environment conducive to expansion and later restrict their numbers by switching asymmetric fates.

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Citations

Jan 29, 2016·Nature Reviews. Molecular Cell Biology·Paulina Strzyz
Mar 12, 2016·Cell·Tianchi XinPeggy Myung
Apr 25, 2016·Journal of Gastroenterology·Huiying MaWendy W J de Leng
Jun 30, 2016·The Journal of Cell Biology·Ellen J EzrattyElaine Fuchs
Aug 16, 2016·Developmental Biology·Sebastian R MerkerDaniel E Stange
Sep 22, 2016·Nature Communications·Ippei KikuchiMasanori Hatakeyama
Apr 28, 2017·Biomaterials Science·Zhichao HaoJun Wu
May 6, 2017·Stem Cells International·Pedro M Aponte, Andrés Caicedo
Feb 27, 2018·Nature Reviews. Genetics·Yejing Ge, Elaine Fuchs
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Jun 1, 2017·Development·Marika Kapsimali
Nov 23, 2016·EMBO Reports·Angela SantoroMarina Mapelli
Dec 14, 2019·ELife·Kendall J LoughScott E Williams
Jan 24, 2020·Biological Reviews of the Cambridge Philosophical Society·Richard W ClaytonRalf Paus
May 17, 2019·Nature·Stephanie J EllisElaine Fuchs
Mar 20, 2019·Experimental Dermatology·Nivedita SaxenaMichael Rendl
Feb 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yejing GeElaine Fuchs
Aug 9, 2020·Frontiers in Physiology·Isabel Mogollón, Laura Ahtiainen
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Jan 10, 2021·International Journal of Molecular Sciences·Jaroslav Mokry, Rishikaysh Pisal

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