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Publication : Hair follicle stem cells regulate retinoid metabolism to maintain the self-renewal niche for melanocyte stem cells.

First Author  Lu Z Year  2020
Journal  Elife Volume  9
PubMed ID  31898934 Mgi Jnum  J:285989
Mgi Id  MGI:6401413 Doi  10.7554/eLife.52712
Citation  Lu Z, et al. (2020) Hair follicle stem cells regulate retinoid metabolism to maintain the self-renewal niche for melanocyte stem cells. Elife 9:e52712
abstractText  Metabolites are major biological parameters sensed by many cell types in vivo, whether they function as signaling mediators of SC and niche cross talk to regulate tissue regeneration is largely unknown. We show here that deletion of the Notch pathway co-factor RBP-J specifically in mouse HFSCs triggers adjacent McSCs to precociously differentiate in their shared niche. Transcriptome screen and in vivo functional studies revealed that the elevated level of retinoic acid (RA) caused by de-repression of RA metabolic process genes as a result of RBP-J deletion in HFSCs triggers ectopic McSCs differentiation in the niche. Mechanistically the increased level of RA sensitizes McSCs to differentiation signal KIT-ligand by increasing its c-Kit receptor protein level in vivo. Using genetic approach, we further pinpointed HFSCs as the source of KIT-ligand in the niche. We discover that HFSCs regulate the metabolite RA level in vivo to allow self-renewal of neighboring McSCs.
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