论文标题：Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy

期刊：Nature Communications

作者：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

发表时间：2019/08/27

数字识别码： 10.1038/s41467-019-11665-0

微信链接：https://mp.weixin.qq.com/s/SxU1cVlIJ1kqAt64qbR-mw

本周《自然-通讯》发表的一篇论文Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy 报道了化疗诱导的永久性脱发的背后机制。研究人员利用小鼠模型和人类毛囊，鉴定出了化疗引起的毛囊干细胞变化——这种变化可引起永久性脱发。

图1：经过Bu/Cy化疗后造成毛囊再生能力的永久性损失.来源：Kim等

和许多成体干细胞一样，毛囊维持着一个再生细胞池，但这些再生细胞会因化疗受损。在因化疗发生脱发后，毛囊干细胞最终可以恢复并重新长出头发。但是，部分化疗会导致干细胞池损失，引起永久性脱发。

韩国首尔国立大学医学院的Ohsang Kwon及同事将人类毛囊移植到无毛小鼠身上，建立了一个化疗诱导的永久性脱发模型。之后，小鼠接受了与人类永久性脱发相关的两步化疗方案。作者发现第一步治疗引起了细胞增殖，第二步治疗引起了大规模细胞死亡。由此导致的干细胞耗竭阻碍了毛发再生。他们提供证据表明，细胞在增殖时对DNA损伤更加敏感，这引起细胞分裂问题，最终导致细胞死亡。

以上发现阐明了化疗诱导的永久性脱发的原因，或许可用于开发预防性疗法。

摘要：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.

（来源：科学网）