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Publication : Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices.

First Author  Yang H Year  2017
Journal  Cell Volume  169
Issue  3 Pages  483-496.e13
PubMed ID  28413068 Mgi Jnum  J:241508
Mgi Id  MGI:5902870 Doi  10.1016/j.cell.2017.03.038
Citation  Yang H, et al. (2017) Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices. Cell 169(3):483-496.e13
abstractText  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.
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