Principles and mechanisms of regeneration in the mouse model for wound‐induced hair follicle neogenesis

Regeneration

Xiaojie Wang¹  Tsai-Ching Hsi¹  Christian Fernando Guerrero-Juarez¹  Kim Pham¹  Kevin Cho¹  Catherine D. McCusker¹  Edwin S. Monuki¹  Ken W.Y. Cho¹  Denise L. Gay² 

[1] Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA;UMR 967, Cellules Souches et Radiations, CEA – INSERM – Universités Paris 7 et Paris 11, CEA/DSV/IRCM/SCSR/LRTS, France

关键词: Hair follicle;    mouse;    neogenesis;    regeneration;    skin;    WNT;    wound;   

DOI  :  10.1002/reg2.38

来源: Wiley

【 摘 要 】

Abstract

Wound-induced hair follicle neogenesis (WIHN) describes a regenerative phenomenon in adult mammalian skin wherein fully functional hair follicles regenerate de novo in the center of large excisional wounds. Originally described in rats, rabbits, sheep, and humans in 1940−1960, the WIHN phenomenon was reinvestigated in mice only recently. The process of de novo hair regeneration largely duplicates the morphological and signaling features of normal embryonic hair development. Similar to hair development, WIHN critically depends on the activation of canonical WNT signaling. However, unlike hair development, WNT activation in WIHN is dependent on fibroblast growth factor 9 signaling generated by the immune system's γδ T cells. The cellular bases of WIHN remain to be fully characterized; however, the available evidence leaves open the possibility for a blastema-like mechanism wherein epidermal and/or dermal wound cells undergo epigenetic reprogramming toward a more plastic, embryonic-like state. De novo hair follicles do not regenerate from preexisting hair-fated bulge stem cells. This suggests that hair neogenesis is not driven by preexisting lineage-restricted progenitors, as is the case for amputation-induced mouse digit tip regeneration, but rather may require a blastema-like mechanism. The WIHN model is characterized by several intriguing features, which await further explanation. These include (1) the minimum wound size requirement for activating neogenesis, (2) the restriction of hair neogenesis to the wound's center, and (3) imperfect patterning outcomes, both in terms of neogenic hair positioning within the wound and in terms of their orientation. Future enquiries into the WIHN process, made possible by a wide array of available skin-specific genetic tools, will undoubtedly expand our understanding of the regeneration mechanisms in adult mammals.

【 授权许可】

CC BY   
© 2015 The Authors. Regeneration published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.