Hair follicle stem cells regulate retinoid metabolism to maintain the self-renewal niche for melanocyte stem cells
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.
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
National key R&D Program of China (2017YFA0103500)
- Zhiwei Lu
National Basic Research Program of China 973 Programs (2014CB849602)
- Zhiwei Lu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Biological Sciences. All of the animals were handled according to the guidelines of the Chinese law regulating the usage of experimental animals and the protocols (M0020) approved by the Committee on the Ethics of Animal Experiments of the National Institute of Biological Sciences, Beijing.
- Valerie Horsley, Yale University, United States
- Received: October 14, 2019
- Accepted: January 3, 2020
- Accepted Manuscript published: January 3, 2020 (version 1)
- Version of Record published: January 20, 2020 (version 2)
© 2020, Lu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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