Single-Cell Transcriptomics Reveals Hair Growth Retardation Mediated by Aberrant Connective Tissue Sheath Contraction in Male Androgenetic Alopecia

February 2026 in “ Nature Communications ”

Guo Li, L.I. Yang, Shixin Duan, Ben Wang, Yujin Zhang, Fangfen Liu, Yunying Wang, Jiayun Li, San Xu, Zheng Wu, Mei Wang, Ben Wang, Zhixiang Zhao, Wei Shi, Mingxing Lei, Hongfu Xie, Yan Tang, Zhili Deng, Ji Li

androgenetic alopecia connective tissue sheath PIEZO1 hair follicle progenitor cells hair follicle miniaturization ML-7 myosin light chain kinase inhibitor AGA

TLDR Inhibiting connective tissue sheath contraction may improve hair growth in male pattern baldness.

This study investigates the cellular mechanisms behind male androgenetic alopecia (AGA) using spatial and single-cell transcriptomics. It identifies that hypercontractility of the connective tissue sheath (CTS) in hair follicles activates the mechanosensitive channel PIEZO1, leading to apoptosis of hair follicle progenitor cells and reduced cell proliferation. This process contributes to hair follicle miniaturization. The study demonstrates that inhibiting CTS contraction with ML-7, a myosin light chain kinase inhibitor, can improve hair follicle growth in both ex vivo models and humanized mice. These findings highlight the peri-follicular CTS as a potential therapeutic target for treating AGA.

View this study on nature.com →

Discuss this study in the Community →

Research cited in this study

41 / 41 results

research Androgenetic Alopecia

October 2025 in “Nature Reviews Disease Primers”

research Fibroblast Bioelectric Signaling Drives Hair Growth

3 citations , August 2025 in “Cell”

Fibroblast bioelectric signaling can promote hair growth and may help treat hair loss.

research Frontiers in the Physiology of Male Pattern Androgenetic Alopecia: Beyond the Androgen Horizon

July 2025 in “Physiological Reviews”

The exact cause of male pattern baldness is unclear, but it may involve factors beyond androgens, offering new treatment possibilities.

research Topical Minoxidil Rejuvenates Hair Follicles in Men with Androgenetic Alopecia In Vivo

June 2024 in “Acta dermato-venereologica”

Topical minoxidil effectively stimulates hair growth in men with hair loss.

research The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia

February 2024 in “International Journal of Molecular Sciences”

Hair loss in Androgenetic Alopecia is caused by genetics, aging, and lifestyle, leading to hair follicle shrinkage and related health risks.

Vellus-To-Terminal Hair Follicle Reconversion Occurs In Male Pattern Balding And Is Promoted By Minoxidil And Platelet-Rich Plasma: In Vivo Evidence From A New Humanized Mouse Model Of Androgenetic Alopecia

research Vellus-To-Terminal Hair Follicle Reconversion Occurs In Male Pattern Balding And Is Promoted By Minoxidil And Platelet-Rich Plasma: In Vivo Evidence From A New Humanized Mouse Model Of Androgenetic Alopecia

October 2023 in “Acta dermato-venereologica”

Minoxidil and platelet-rich plasma can help turn thin hair into thicker hair in male pattern baldness.

research Androgenetic Alopecia: An Update

July 2023 in “JAAD International”

Two drugs, finasteride and minoxidil, are approved for hair loss treatment, but new therapies are being developed.

research Androgenetic Alopecia: Therapy Update

May 2023 in “Drugs”

There are many treatments for common hair loss, but more trials are needed to decide which are best.

research Single-Cell Transcriptomics Reveals Lineage Trajectory of Human Scalp Hair Follicle and Informs Mechanisms of Hair Graying

13 citations , May 2022 in “Cell discovery”

The study found new details about human hair growth and suggests that preventing a specific biological pathway could potentially treat hair graying.

research Treatment Options for Androgenetic Alopecia: Efficacy, Side Effects, Compliance, Financial Considerations, and Ethics

17 citations , November 2021 in “Journal of Cosmetic Dermatology”

Combination therapies for androgenetic alopecia work best but can have significant side effects and costs.

research Hair Shaft Miniaturization Causes Stem Cell Depletion Through Mechanosensory Signals Mediated by a Piezo1-Calcium-TNF-α Axis

23 citations , October 2021 in “Cell Stem Cell”

Hair thinning causes stem cell loss through a process involving Piezo1, calcium, and TNF-α.

research Health-Related Quality of Life, Depression, and Self-Esteem in Patients With Androgenetic Alopecia

15 citations , July 2021 in “JAMA Dermatology”

Androgenetic alopecia negatively affects quality of life and self-esteem, especially in women, but not depression.

research The Inflammatory Aspect of Male and Female Pattern Hair Loss

9 citations , November 2020 in “Journal of Inflammation Research”

Inflammation affects hair loss; anti-inflammatory treatments may help.

research Functional Complexity of Hair Follicle Stem Cell Niche and Therapeutic Targeting of Niche Dysfunction for Hair Regeneration

59 citations , March 2020 in “Journal of Biomedical Science”

Understanding how hair follicle stem cells work can help find new ways to prevent hair loss and promote hair growth.

research Post-Finasteride Syndrome: An Emerging Clinical Problem

26 citations , December 2019 in “Neurobiology of Stress”

Post-finasteride syndrome causes lasting sexual, neurological, and physical side effects in some people after taking finasteride.

research Physiopathology and Current Treatments of Androgenetic Alopecia: Going Beyond Androgens and Anti-Androgens

45 citations , August 2019 in “Dermatologic Therapy”

Hair loss treatments work better with lifestyle changes.

HRQoL in Hair Loss-Affected Patients with Alopecia Areata, Androgenetic Alopecia, and Telogen Effluvium: The Role of Personality Traits and Psychosocial Anxiety

research HRQoL in Hair Loss-Affected Patients with Alopecia Areata, Androgenetic Alopecia, and Telogen Effluvium: The Role of Personality Traits and Psychosocial Anxiety

29 citations , November 2018 in “Journal of The European Academy of Dermatology and Venereology”

Personality traits and anxiety affect hair loss patients' quality of life.

research Psychological Assessment in 355 Chinese College Students With Androgenetic Alopecia

11 citations , August 2018 in “Medicine”

Hair loss in Chinese college students leads to various psychological issues, so treatment should address both hair loss and mental health.

research Androgenetic Alopecia: Drug Safety and Therapeutic Strategies

20 citations , January 2018 in “Expert Opinion on Drug Safety”

Personalized treatment with inhibitors, minoxidil, and laser therapy helps hair loss.

research Genetic and Molecular Aspects of Androgenetic Alopecia

24 citations , January 2018 in “Indian Journal of Dermatology, Venereology and Leprology”

Androgenetic alopecia is mainly caused by genetic factors and increased androgen activity, leading to hair follicle miniaturization.

Divergent Proliferation Patterns of Distinct Human Hair Follicle Epithelial Progenitor Niches In Situ and Their Differential Responsiveness to Prostaglandin D2

research Divergent Proliferation Patterns of Distinct Human Hair Follicle Epithelial Progenitor Niches In Situ and Their Differential Responsiveness to Prostaglandin D2

21 citations , November 2017 in “Scientific Reports”

Different human hair follicle stem cells grow at different rates and respond differently to a baldness-related compound.

research The Effectiveness of Treatments for Androgenetic Alopecia: A Systematic Review and Meta-Analysis

178 citations , April 2017 in “Journal of The American Academy of Dermatology”

Minoxidil, finasteride, and low-level laser light therapy effectively treat hair loss.

research Epithelial-Mesenchymal Micro-Niches Govern Stem Cell Lineage Choices

214 citations , April 2017 in “Cell”

Different small areas within hair follicles send specific signals that control what type of cells stem cells become.

research Androgenetic Alopecia: A Review

153 citations , March 2017 in “Endocrine”

Male pattern baldness involves genetics, hormones, and needs better treatments.

research Hair Follicle Aging Is Driven by Transepidermal Elimination of Stem Cells via COL17A1 Proteolysis

242 citations , February 2016 in “Science”

Hair loss and aging are caused by the breakdown of a key protein in hair stem cells.

research Hunting the Genes in Male-Pattern Alopecia: How Important Are They, How Close Are We and What Will They Tell Us?

46 citations , February 2016 in “Experimental Dermatology”

Genes play a significant role in male-pattern baldness, and understanding them could lead to new treatments and insights into related health issues.

research A Guide to Studying Human Hair Follicle Cycling In Vivo

212 citations , September 2015 in “Journal of Investigative Dermatology”

The document provides a method to classify human hair growth stages using a model with human scalp on mice, aiming to standardize hair research.

research Androgenetic Alopecia: New Insights Into the Pathogenesis and Mechanism of Hair Loss

33 citations , August 2015 in “F1000Research”

New model shows muscle affects hair loss differently in men and women.

research Human Hair Follicle Organ Culture: Theory, Application, and Perspectives

130 citations , August 2015 in “Experimental Dermatology”

Human hair follicle organ culture is a useful model for hair research with potential for studying hair biology and testing treatments.

research mTOR Signaling Promotes Stem Cell Activation via Counterbalancing BMP-Mediated Suppression During Hair Regeneration

71 citations , January 2015 in “Journal of molecular cell biology/Journal of Molecular Cell Biology”

mTOR signaling helps activate hair stem cells by balancing out the suppression caused by BMP during hair growth.

research Hair Follicle Dermal Stem Cells Regenerate the Dermal Sheath, Repopulate the Dermal Papilla, and Modulate Hair Type

184 citations , November 2014 in “Developmental Cell”

Hair follicle dermal stem cells are key for regenerating parts of the hair follicle and determining hair type.

The Dermal Papilla: An Instructive Niche for Epithelial Stem and Progenitor Cells in Development and Regeneration of the Hair Follicle

research The Dermal Papilla: An Instructive Niche for Epithelial Stem and Progenitor Cells in Development and Regeneration of the Hair Follicle

149 citations , July 2014 in “Cold Spring Harbor Perspectives in Medicine”

The dermal papilla is crucial for hair growth and health, and understanding it could lead to new hair loss treatments.

research Macroenvironmental Regulation of Hair Cycling and Collective Regenerative Behavior

42 citations , January 2014 in “Cold Spring Harbor Perspectives in Medicine”

Hair growth is influenced by various body and external factors, and neighboring hairs communicate to synchronize regeneration.

research New Activators and Inhibitors in the Hair Cycle Clock: Targeting Stem Cells’ State of Competence

68 citations , April 2012 in “Journal of Investigative Dermatology”

The conclusion is that Fgf18 and Tgf-ß signaling could be targeted for hair loss treatments.

research Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

499 citations , September 2011 in “Cell”

Fat-related cells are important for initiating hair growth.

Bald Scalp in Men with Androgenetic Alopecia Retains Hair Follicle Stem Cells but Lacks CD200-Rich and CD34-Positive Hair Follicle Progenitor Cells

research Bald Scalp in Men with Androgenetic Alopecia Retains Hair Follicle Stem Cells but Lacks CD200-Rich and CD34-Positive Hair Follicle Progenitor Cells

235 citations , January 2011 in “Journal of Clinical Investigation”

Men with baldness due to androgenetic alopecia still have hair stem cells, but lack specific cells needed for hair growth.

research Molecular Basis of Androgenetic Alopecia: From Androgen to Paracrine Mediators Through Dermal Papilla

122 citations , November 2010 in “Journal of Dermatological Science”

Male pattern baldness involves hormones and cell signals affecting hair growth.

research Methods in Hair Research: How to Objectively Distinguish Between Anagen and Catagen in Human Hair Follicle Organ Culture

132 citations , September 2009 in “Experimental Dermatology”

A reliable system was developed to distinguish hair growth stages, aiding in identifying hair growth promoters or inhibitors.

research Burden of Hair Loss: Stress and the Underestimated Psychosocial Impact of Telogen Effluvium and Androgenetic Alopecia

162 citations , August 2004 in “Journal of Investigative Dermatology”

Hair loss causes stress and affects mental health; treatment and support needed.

research Possible Mechanisms of Miniaturization During Androgenetic Alopecia or Pattern Hair Loss

116 citations , September 2001 in “Journal of The American Academy of Dermatology”

Hair loss occurs due to fewer papillary cells, smaller follicles, and shorter growth phases.

research The Psychosocial Consequences of Androgenetic Alopecia: A Review of the Research Literature

180 citations , September 1999 in “British Journal of Dermatology”

Hair loss affects self-esteem and quality of life; treatments can help.

Similar Research

5 / 1000+ results

Aberrant Connective Tissue Sheath Contraction Drives Premature Hair Follicle Regression by Inducing Progenitor Cell Depletion in Androgenetic Alopecia

research Aberrant Connective Tissue Sheath Contraction Drives Premature Hair Follicle Regression by Inducing Progenitor Cell Depletion in Androgenetic Alopecia

December 2023 in “bioRxiv (Cold Spring Harbor Laboratory)”

Abnormal contraction of connective tissue in hair follicles causes hair loss by killing off important cells, and treating this could improve hair growth.

research Hair Shaft Miniaturization Causes Stem Cell Depletion Through Mechanosensory Signals Mediated by a Piezo1-Calcium-TNF-α Axis

23 citations , October 2021 in “Cell Stem Cell”

Hair thinning causes stem cell loss through a process involving Piezo1, calcium, and TNF-α.