Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells

How to elicit and harness regeneration is a major issue in wound healing. Skin injury in most amniotes leads to repair rather than regeneration, except in hair and feathers. Feather follicles are unique organs that undergo physiological cyclic renewal, supported by a dynamic stem cell niche. During...

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Main Authors: Ting-Xin Jiang, Ping Wu, Ang Li, Randall B. Widelitz, Cheng-Ming Chuong
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Journal of Developmental Biology
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Online Access:https://www.mdpi.com/2221-3759/13/2/10
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author Ting-Xin Jiang
Ping Wu
Ang Li
Randall B. Widelitz
Cheng-Ming Chuong
author_facet Ting-Xin Jiang
Ping Wu
Ang Li
Randall B. Widelitz
Cheng-Ming Chuong
author_sort Ting-Xin Jiang
collection DOAJ
description How to elicit and harness regeneration is a major issue in wound healing. Skin injury in most amniotes leads to repair rather than regeneration, except in hair and feathers. Feather follicles are unique organs that undergo physiological cyclic renewal, supported by a dynamic stem cell niche. During normal feather cycling, growth-phase proximal follicle collar bulge stem cells adopt a ring configuration. At the resting and initiation phases, these stem cells descend to the dermal papilla to form papillary ectoderm and ascend to the proximal follicle in a new growth phase. Plucking resting-phase feathers accelerates papillary ectoderm cell activation. Plucking growth-phase feathers depletes collar bulge stem cells; however, a blastema reforms the collar bulge stem cells, expressing KRT15, LGR6, Sox9, integrin-α6, and tenascin C. Removing the follicle base and dermal papilla prevents feather regeneration. Yet, transplanting an exogenous dermal papilla to the follicle base can induce re-epithelialization from the lower follicle sheath, followed by feather regeneration. Thus, there is a stepwise regenerative strategy using stem cells located in the collar bulge, papillary ectoderm, and de-differentiated lower follicle sheath to generate new feathers after different levels of injuries. This adaptable regenerative mechanism is based on the hierarchy of stem cell regenerative capacity and underscores the remarkable resilience of feather follicle regenerative abilities.
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spelling doaj-art-5412c78b74a2492491f6ac4f4b3e7cc82025-06-25T13:59:12ZengMDPI AGJournal of Developmental Biology2221-37592025-03-011321010.3390/jdb13020010Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem CellsTing-Xin Jiang0Ping Wu1Ang Li2Randall B. Widelitz3Cheng-Ming Chuong4Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USADepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USADepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USADepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USADepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USAHow to elicit and harness regeneration is a major issue in wound healing. Skin injury in most amniotes leads to repair rather than regeneration, except in hair and feathers. Feather follicles are unique organs that undergo physiological cyclic renewal, supported by a dynamic stem cell niche. During normal feather cycling, growth-phase proximal follicle collar bulge stem cells adopt a ring configuration. At the resting and initiation phases, these stem cells descend to the dermal papilla to form papillary ectoderm and ascend to the proximal follicle in a new growth phase. Plucking resting-phase feathers accelerates papillary ectoderm cell activation. Plucking growth-phase feathers depletes collar bulge stem cells; however, a blastema reforms the collar bulge stem cells, expressing KRT15, LGR6, Sox9, integrin-α6, and tenascin C. Removing the follicle base and dermal papilla prevents feather regeneration. Yet, transplanting an exogenous dermal papilla to the follicle base can induce re-epithelialization from the lower follicle sheath, followed by feather regeneration. Thus, there is a stepwise regenerative strategy using stem cells located in the collar bulge, papillary ectoderm, and de-differentiated lower follicle sheath to generate new feathers after different levels of injuries. This adaptable regenerative mechanism is based on the hierarchy of stem cell regenerative capacity and underscores the remarkable resilience of feather follicle regenerative abilities.https://www.mdpi.com/2221-3759/13/2/10skin appendagesdermal papillawoundingregenerationstem cellsfeather cycling
spellingShingle Ting-Xin Jiang
Ping Wu
Ang Li
Randall B. Widelitz
Cheng-Ming Chuong
Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells
Journal of Developmental Biology
skin appendages
dermal papilla
wounding
regeneration
stem cells
feather cycling
title Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells
title_full Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells
title_fullStr Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells
title_full_unstemmed Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells
title_short Wound-Induced Regeneration in Feather Follicles: A Stepwise Strategy to Regenerate Stem Cells
title_sort wound induced regeneration in feather follicles a stepwise strategy to regenerate stem cells
topic skin appendages
dermal papilla
wounding
regeneration
stem cells
feather cycling
url https://www.mdpi.com/2221-3759/13/2/10
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AT angli woundinducedregenerationinfeatherfolliclesastepwisestrategytoregeneratestemcells
AT randallbwidelitz woundinducedregenerationinfeatherfolliclesastepwisestrategytoregeneratestemcells
AT chengmingchuong woundinducedregenerationinfeatherfolliclesastepwisestrategytoregeneratestemcells