Hair Bulge Stem Cells Share a Tendon Stem Cell Lineage
Shailesh Agarwal, MD, Michael Sorkin, MD, Shawn Loder, BS, David Cholok, BS, Joshua Peterson, BS, Paul Cederna, MD, Ernestina Schipani, MD, PhD, Benjamin Levi, MD.
University of Michigan, Ann Arbor, MI, USA.
PURPOSE: Hair bulge stem cells (HBSCs) contribute to wound healing, prompting interest in their identification and functional analysis. We show that HBSCs share a lineage with tendon stem cells, consistent with the proximity between the bulge and arrector pilli muscle.
METHODS: Scx-cre/ROSAHIF2fl/fl mice were created to study BMP signaling and hypoxia inducible factor-2 (HIF2) in tendon development. Mice were incidentally noted to progressively lose dorsal hair, prompting evaluation of Scx-cre within skin and hair follicles using Scx-cre/ROSA26mTmG lineage-tracing mice. Mechanism for hair loss was probed using immunostaining for phospho-SMAD1/5, a mediator of the hair cycle and BMP signaling.
RESULTS: Scx-cre/ROSAHIF2fl/fl mice develop their first coat normally followed by gradual loss apparent by 14 days after birth (A); Scx-cre/BMPR1afl/fl lose their hair within their first week. Scx-cre/ROSA26mTmG lineage-tracing mice confirmed that the hair bulge was partially marked by cells of a tendon lineage (Scx-cre) (B,C). Within the skin, these cells were localized to the hair bulge. Histologic sectioning of skin from 4-week old mice show increased pSMAD 1/5 expression within the bulge (D).
CONCLUSION: Our findings confirm that cells of a tendon lineage reside within the hair bulge, and that these cells can regulate hair development and cycling. This unique model also suggests a previously undescribed relationship between HIF2 and pSMAD1/5 signaling. Future studies will determine whether Scx-cre cells directly contribute to wound healing and hair regeneration.
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