@article{aac480565679454998dc8688118ddf5e,
title = "Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells",
abstract = "Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study interactions across epithelium, mesenchyme, and nerves. Here, we show that APMs and sympathetic nerves form a dual-component niche to modulate hair follicle stem cell (HFSC) activity. Sympathetic nerves form synapse-like structures with HFSCs and regulate HFSCs through norepinephrine, whereas APMs maintain sympathetic innervation to HFSCs. Without norepinephrine signaling, HFSCs enter deep quiescence by down-regulating the cell cycle and metabolism while up-regulating quiescence regulators Foxp1 and Fgf18. During development, HFSC progeny secretes Sonic Hedgehog (SHH) to direct the formation of this APM-sympathetic nerve niche, which in turn controls hair follicle regeneration in adults. Our results reveal a reciprocal interdependence between a regenerative tissue and its niche at different stages and demonstrate sympathetic nerves can modulate stem cells through synapse-like connections and neurotransmitters to couple tissue production with demands.",
keywords = "Adrb2, hair follicle stem cells, nerve-stem-cell interaction, niche, stem cell quiescence, sympathetic nerve",
author = "Yulia Shwartz and Meryem Gonzalez-Celeiro and Chen, {Chih Lung} and Pasolli, {H. Amalia} and Sheu, {Shu Hsien} and Fan, {Sabrina Mai Yi} and Farnaz Shamsi and Steven Assaad and Lin, {Edrick Tai Yu} and Bing Zhang and Tsai, {Pai Chi} and Megan He and Tseng, {Yu Hua} and Lin, {Sung Jan} and Hsu, {Ya Chieh}",
note = "Funding Information: We thank G. Karsenty for Adrb2 fl/fl mice, D. Ginty, C. Harwell, and L. Orefice for the Avil-Cre; Shh fl/fl mice, and many colleagues who donated mice to JAX; Y. Fong, C. Huang, D. Ginty, L. Orefice, and X. Jin for comments on the manuscript; N. Alharbi, S. Kim, S. Tham, Y.-L. Kang, HCBI, HSCRB FACS core, HMS EM facility, HSCRB histology core, and NTUH 2nd and 8th core labs for technical support; A. Shwartz for assistance with imaging analyses; G. Kidd and E. Benson for block face scanning EM; and Transgenic Mouse Core Lab, National Taiwan University Centers of Genomic and Precision Medicine for generation of the SMA-YFP-DTR transgenic mouse line. This work was supported by the New York Stem Cell Foundation , the Smith Family Foundation Odyssey Award , the Pew Charitable Trusts , the Harvard NeuroDiscovery Center , the Harvard Stem Cell Institute , the Harvard Medical School Dean{\textquoteright}s Innovation Grant , the American Cancer Society ( RSG-18-152-01-DDC ), the NIH ( R01-AR070825 to Y.-C.H. and R01DK077097 and R01DK102898 to Y.-H.T.), the Taiwan Ministry of Science and Technology ( 107-2314-B-002-064-MY3 to S.-J.L.), and the National Taiwan University Hospital ( UN107-005 , 107S3781 , UN108-029 , and UN109-005 to S.-J.L.). Y.-C.H. is a Pew Scholar and a NYSCF – Robertson Investigator . S.-J.L. is a Taiwan Bio-Development Foundation (TBF) Chair in Biotechnology. Y.S. is a Helen Hay Whitney postdoctoral fellow and receives the Women in Science Weizmann Institute of Science Award . M.G.-C. and M.H. are recipients of the Simmons Family Award . F.S. is supported by the American Diabetes Association grant ( 1-18-PDF-169 ). B.Z. is awarded with the Charles A. King Trust Postdoctoral Research Fellowship . M.H is supported by the NSF Graduate Research Fellowships Program ( DGE1745303 ). Funding Information: We thank G. Karsenty for Adrb2 fl/fl mice, D. Ginty, C. Harwell, and L. Orefice for the Avil-Cre; Shh fl/fl mice, and many colleagues who donated mice to JAX; Y. Fong, C. Huang, D. Ginty, L. Orefice, and X. Jin for comments on the manuscript; N. Alharbi, S. Kim, S. Tham, Y.-L. Kang, HCBI, HSCRB FACS core, HMS EM facility, HSCRB histology core, and NTUH 2nd and 8th core labs for technical support; A. Shwartz for assistance with imaging analyses; G. Kidd and E. Benson for block face scanning EM; and Transgenic Mouse Core Lab, National Taiwan University Centers of Genomic and Precision Medicine for generation of the SMA-YFP-DTR transgenic mouse line. This work was supported by the New York Stem Cell Foundation, the Smith Family Foundation Odyssey Award, the Pew Charitable Trusts, the Harvard NeuroDiscovery Center, the Harvard Stem Cell Institute, the Harvard Medical School Dean's Innovation Grant, the American Cancer Society (RSG-18-152-01-DDC), the NIH (R01-AR070825 to Y.-C.H. and R01DK077097 and R01DK102898 to Y.-H.T.), the Taiwan Ministry of Science and Technology (107-2314-B-002-064-MY3 to S.-J.L.), and the National Taiwan University Hospital (UN107-005, 107S3781, UN108-029, and UN109-005 to S.-J.L.). Y.-C.H. is a Pew Scholar and a NYSCF ? Robertson Investigator. S.-J.L. is a Taiwan Bio-Development Foundation (TBF) Chair in Biotechnology. Y.S. is a Helen Hay Whitney postdoctoral fellow and receives the Women in Science Weizmann Institute of Science Award. M.G.-C. and M.H. are recipients of the Simmons Family Award. F.S. is supported by the American Diabetes Association grant (1-18-PDF-169). B.Z. is awarded with the Charles A. King Trust Postdoctoral Research Fellowship. M.H is supported by the NSF Graduate Research Fellowships Program (DGE1745303). Experiment Design, Y.S. M.G.-C. C.-L.C. Y.-C.H. and S.-J.L.; Experiments, Y.S. M.G.-C. C-L.C. S.M.-Y.F. P.-C.T. B.Z. F.S. S.A. E.T.-Y.L. and M.H.; Intellectual Contributions, Y-C.H. S-J.L. M.G.-C. Y.S. C-L.C. H.A.P. S.-H.S. and Y.-H.T.; Manuscript Writing, Y.-C.H, Y.S. M.G.-C. and S.-J.L. with input from all authors. A provisional patent application has been filed by the President and Fellows of Harvard College based on this work. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = aug,
day = "6",
doi = "10.1016/j.cell.2020.06.031",
language = "English (US)",
volume = "182",
pages = "578--593.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}