Hair follicles' transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog.
Growth and regeneration of one tissue within an organ compels accommodative changes in the surrounding tissues. However, the molecular nature and operating logic governing these concurrent changes remain poorly defined. The dermal adipose layer expands concomitantly with hair follicle downgrowth, providing a paradigm for studying coordinated changes of surrounding lineages with a regenerating tissue. Here, we discover that hair follicle transit-amplifying cells (HF-TACs) play an essential role in orchestrating dermal adipogenesis through secreting Sonic Hedgehog (SHH). Depletion of Shh from HF-TACs abrogates both dermal adipogenesis and hair follicle growth. Using cell type-specific deletion of Smo, a gene required in SHH-receiving cells, we found that SHH does not act on hair follicles, adipocytes, endothelial cells, and hematopoietic cells for adipogenesis. Instead, SHH acts directly on adipocyte precursors, promoting their proliferation and their expression of a key adipogenic gene, peroxisome proliferator-activated receptor γ (Pparg), to induce dermal adipogenesis. Our study therefore uncovers a critical role for TACs in orchestrating the generation of both their own progeny and a neighboring lineage to achieve concomitant tissue production across lineages.
Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Bing
B
Zhang
Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Pai-Chi
PC
Tsai
Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.|Institute of Molecular Health Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland.
Meryem
M
Gonzalez-Celeiro
Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Oliver
O
Chung
Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Benjamin
B
Boumard
Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Carolina N
CN
Perdigoto
Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Elena
E
Ezhkova
Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Ya-Chieh
YC
Hsu
D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D015398:Signal Transduction; D012867:Skin / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*
D053823:Hedgehog Proteins; C465570:Shh protein, mouse
adipocyte precursors; adipogenesis; hair follicle regeneration; interlineage communications; stroma; transit-amplifying cells