Παρασκευή 14 Απριλίου 2017

Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices

Publication date: Available online 13 April 2017
Source:Cell
Author(s): Hanseul Yang, Rene C. Adam, Yejing Ge, Zhong L. Hua, Elaine Fuchs
Adult tissue stem cells (SCs) reside in niches, which, through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single-cell RNA-seq, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage tracing, temporal single-cell analyses, and chromatin landscaping, we show that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged unilineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: some progenitors specify lineages immediately, whereas others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment.

Graphical abstract

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Teaser

Stem cells and their short lived proliferative progeny exhibit molecular heterogeneity set up by micro-niches in the regenerating hair follicle.


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