Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology (CDB) and RIKEN Center for Biosystems Dynamics Research (BDR), Hyogo, 650-0047, Japan.
Organ Technologies Inc., Tokyo, 101-0048, Japan.
Sci Rep. 2021 Feb 10;11(1):1173. doi: 10.1038/s41598-020-80624-3.
In mammals, organ induction occurs only during embryonic development except for hair follicles (HFs). However, HF-resident epithelial stem cells (HFSCs), which are responsible for repetitive HF regeneration, are not fully characterized. Here, we establish in vitro culture systems that are capable of controlling the ability of HFSCs to regenerate HFs. Based on a method that precisely controlled the number of HFs for regeneration, functional analysis revealed that CD34/CD49f/integrin β5 (Itgβ5)-triple-positive (CD34+/CD49f+/Itgβ5+) cells have multipotency and functional significance for continual hair regeneration. In native HFs, these cells reside in the uppermost area of the bulge region, which is surrounded by tenascin in mice and humans. This study unveils the subpopulation of HFSCs responsible for long-term hair cycling of HFs regenerated from bioengineered HF germ, suggesting the presence of functional heterogeneity among bulge HFSCs and the utility of our culture system to achieve HF regenerative therapy.
在哺乳动物中，器官诱导仅发生在胚胎发育过程中，除了毛囊 (HFs)。然而，负责反复 HFs 再生的 HFs 驻留上皮干细胞 (HFSCs) 尚未得到充分表征。在这里，我们建立了体外培养系统，能够控制 HFSCs 再生 HFs 的能力。基于一种精确控制 HFs 再生数量的方法，功能分析表明 CD34/CD49f/整合素 β5 (Itgβ5)-三阳性 (CD34+/CD49f+/Itgβ5+) 细胞具有多能性和对持续毛发再生的功能意义。在天然 HFs 中，这些细胞位于毛囊隆起区域的最上部，在小鼠和人类中，该区域被 tenascin 包围。这项研究揭示了负责从生物工程 HFs 生殖中再生的 HFs 长期毛发循环的 HFSCs 亚群，表明隆起 HFSCs 之间存在功能异质性，以及我们的培养系统在实现 HFs 再生治疗方面的实用性。
