Hair follicles’ transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog

¹Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts 02138, USA;
²Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA;
³Institute of Molecular Health Sciences, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland;
⁴Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA;
⁵Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA

Corresponding author:yachieh_hsu{at}harvard.edu

↵6 These authors contributed equally to this work.

Abstract

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 ofShh from HF-TACs abrogates both dermal adipogenesis and hair follicle growth. Using cell type-specific deletion ofSmo, 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.

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Footnotes

Supplemental material is available for this article.
Article published online ahead of print. Article and publication date are online athttp://www.genesdev.org/cgi/doi/10.1101/gad.285429.116.

ReceivedJune 12, 2016.
AcceptedOctober 3, 2016.

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