Format

Send to

Choose Destination
Cancer Res. 2017 Nov 15;77(22):6083-6096. doi: 10.1158/0008-5472.CAN-17-0667. Epub 2017 Sep 22.

Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy.

Huang WY1, Lai SF1,2, Chiu HY1,3,4, Chang M5, Plikus MV6, Chan CC4, Chen YT7, Tsao PN8,9, Yang TL9,10,11, Lee HS12,13, Chi P14,15, Lin SJ16,4,9,11.

Author information

1
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
2
Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
3
Department of Dermatology, Hsin-Chu Branch, National Taiwan University Hospital, Hsin-Chu City, Taiwan.
4
Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
5
Sophie Davis School of Biomedical Education, City University of New York, New York, New York.
6
Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center and Center for Complex Biological Systems, University of California, Irvine, Irvine, California.
7
Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan.
8
Department of Pediatrics, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
9
Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
10
Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
11
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
12
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
13
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
14
Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
15
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
16
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan. drsjlin@ntu.edu.tw.

Abstract

Genotoxicity-induced hair loss from chemotherapy and radiotherapy is often encountered in cancer treatment, and there is a lack of effective treatment. In growing hair follicles (HF), quiescent stem cells (SC) are maintained in the bulge region, and hair bulbs at the base contain rapidly dividing, yet genotoxicity-sensitive transit-amplifying cells (TAC) that maintain hair growth. How genotoxicity-induced HF injury is repaired remains unclear. We report here that HFs mobilize ectopic progenitors from distinct TAC compartments for regeneration in adaptation to the severity of dystrophy induced by ionizing radiation (IR). Specifically, after low-dose IR, keratin 5+ basal hair bulb progenitors, rather than bulge SCs, were quickly activated to replenish matrix cells and regenerated all concentric layers of HFs, demonstrating their plasticity. After high-dose IR, when both matrix and hair bulb cells were depleted, the surviving outer root sheath cells rapidly acquired an SC-like state and fueled HF regeneration. Their progeny then homed back to SC niche and supported new cycles of HF growth. We also revealed that IR induced HF dystrophy and hair loss and suppressed WNT signaling in a p53- and dose-dependent manner. Augmenting WNT signaling attenuated the suppressive effect of p53 and enhanced ectopic progenitor proliferation after genotoxic injury, thereby preventing both IR- and cyclophosphamide-induced alopecia. Hence, targeted activation of TAC-derived progenitor cells, rather than quiescent bulge SCs, for anagen HF repair can be a potential approach to prevent hair loss from chemotherapy and radiotherapy. Cancer Res; 77(22); 6083-96. ©2017 AACR.

PMID:
28939680
PMCID:
PMC5756475
DOI:
10.1158/0008-5472.CAN-17-0667
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center