Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy

Jin Yong Kim, Jungyoon Ohn, Ji Seon Yoon, Bo Mi Kang, Minji Park, Sookyung Kim, Woochan Lee, Sungjoo Hwang, Jong Il Kim, Kyu Han Kim, Ohsang Kwon

Research output: Contribution to journalArticle

Abstract

The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We uncover the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. In contrast to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy.

Original languageEnglish
Article number3694
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019

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priming
Chemotherapy
Hair Follicle
stem cells
hair
chemotherapy
Stem cells
regeneration
Regeneration
Stem Cells
actuators
Drug Therapy
Busulfan
Cyclophosphamide
DNA Damage
Hematopoietic Stem Cell Mobilization
Adult Stem Cells
Alkylating Agents
deoxyribonucleic acid
Phosphatidylinositol 3-Kinases

Cite this

Kim, Jin Yong ; Ohn, Jungyoon ; Yoon, Ji Seon ; Kang, Bo Mi ; Park, Minji ; Kim, Sookyung ; Lee, Woochan ; Hwang, Sungjoo ; Kim, Jong Il ; Kim, Kyu Han ; Kwon, Ohsang. / Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy. / Kim, Jin Yong; Ohn, Jungyoon; Yoon, Ji Seon; Kang, Bo Mi; Park, Minji; Kim, Sookyung; Lee, Woochan; Hwang, Sungjoo; Kim, Jong Il; Kim, Kyu Han; Kwon, Ohsang.

In: Nature Communications, Vol. 10, No. 1, 3694, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Kim, Jin Yong

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AU - Kang, Bo Mi

AU - Park, Minji

AU - Kim, Sookyung

AU - Lee, Woochan

AU - Hwang, Sungjoo

AU - Kim, Jong Il

AU - Kim, Kyu Han

AU - Kwon, Ohsang

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