MicroRNA-205 promotes hair regeneration by modulating mechanical properties of hair follicle stem cells

Author:

Wang Jingjing12ORCID,Fu Yuheng12,Huang Wenmao3ORCID,Biswas Ritusree4,Banerjee Avinanda5,Broussard Joshua A.126,Zhao Zhihai3,Wang Dongmei126ORCID,Bjerke Glen7ORCID,Raghavan Srikala45ORCID,Yan Jie3ORCID,Green Kathleen J.126,Yi Rui126ORCID

Affiliation:

1. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

2. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

3. Mechanobiology Institute, National University of Singapore 117411, Singapore

4. Institute for Stem Cell Science and Regenerative Medicine, GKVK Campus, Bangalore 560065, India

5. A*Star Skin Research Institute of Singapore, Singapore 138648, Singapore

6. Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

7. Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309

Abstract

Stiffness and actomyosin contractility are intrinsic mechanical properties of animal cells required for the shaping of tissues. However, whether tissue stem cells (SCs) and progenitors located within SC niche have different mechanical properties that modulate their size and function remains unclear. Here, we show that hair follicle SCs in the bulge are stiff with high actomyosin contractility and resistant to size change, whereas hair germ (HG) progenitors are soft and periodically enlarge and contract during quiescence. During activation of hair follicle growth, HGs reduce contraction and more frequently enlarge, a process that is associated with weakening of the actomyosin network, nuclear YAP accumulation, and cell cycle reentry. Induction of miR-205 , a novel regulator of the actomyosin cytoskeleton, reduces actomyosin contractility and activates hair regeneration in young and old mice. This study reveals the control of tissue SC size and activities by spatiotemporally compartmentalized mechanical properties and demonstrates the possibility to stimulate tissue regeneration by fine-tuning cell mechanics.

Funder

HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Science Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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