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Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6880-E6889. doi: 10.1073/pnas.1719548115. Epub 2018 Jun 29.

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

Fan SM1, Chang YT2, Chen CL1,3, Wang WH1, Pan MK4,5, Chen WP6, Huang WY1, Xu Z7, Huang HE1, Chen T7, Plikus MV8,9, Chen SK10,11, Lin SJ12,3,11,13,14.

Author information

1
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, 100 Taipei, Taiwan.
2
Department of Life Science, College of Life Science, National Taiwan University, 106 Taipei, Taiwan.
3
Department of Dermatology, National Taiwan University Hospital and College of Medicine, 100 Taipei, Taiwan.
4
Department of Medical Research, National Taiwan University Hospital, 100 Taipei, Taiwan.
5
Department of Neurology, National Taiwan University Hospital, 100 Taipei, Taiwan.
6
Institute of Pharmacology, College of Medicine, National Taiwan University, 100 Taipei, Taiwan.
7
National Institute of Biological Sciences, 102206 Beijing, China.
8
Center for Complex Biological Systems, University of California, Irvine, CA 92697.
9
Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697.
10
Department of Life Science, College of Life Science, National Taiwan University, 106 Taipei, Taiwan; alenskchen@ntu.edu.tw drsjlin@ntu.edu.tw.
11
Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, 100 Taipei, Taiwan.
12
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, 100 Taipei, Taiwan; alenskchen@ntu.edu.tw drsjlin@ntu.edu.tw.
13
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, 100 Taipei, Taiwan.
14
Molecular Imaging Center, National Taiwan University, 100 Taipei, Taiwan.

Abstract

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

KEYWORDS:

circadian rhythm; hair follicle; melanopsin; stem cell; sympathetic nerve

PMID:
29959210
PMCID:
PMC6055137
DOI:
10.1073/pnas.1719548115
[Indexed for MEDLINE]
Free PMC Article

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