小柯机器人

美国纽约大学Mayumi Ito小组发现，去分化使黑色素细胞干细胞保持在一个动态微环境中。2023年4月19日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表明大多数黑色素细胞干细胞（McSC）在自我更新和生成成熟后代的过程中，会在转运扩增和干细胞状态之间切换，这种机制与其他自我更新系统的机制根本不同。活体成像和单细胞RNA测序显示，McSC是流动的，在毛囊干细胞和过渡增殖区之间转换，在那里它们可逆地进入受局部微环境线索（如WNT）支配的不同分化状态。长期的系谱追踪表明，McSC系统是由可逆的McSC而不是由固有的免于可逆变化的保留干细胞维持的。在老化过程中,搁浅的McSC不断累积,对黑色素细胞后代的再生没有贡献。这些结果确定了一个新的模型，即去分化是平衡干细胞维护的组成部分，并表明调节McSC的流动性可能是预防头发变白的一个新方法。

据悉，由于未知的原因，McSC系统比其他成人干细胞群更早失效，这导致大多数人类和小鼠的毛发变白。目前的范式指出，McSC在毛囊微环境中处于未分化状态，与分化的后代物理隔离，并在再生刺激的提示下迁移。

附：英文原文

Title: Dedifferentiation maintains melanocyte stem cells in a dynamic niche

Author: Sun, Qi, Lee, Wendy, Hu, Hai, Ogawa, Tatsuya, De Leon, Sophie, Katehis, Ioanna, Lim, Chae Ho, Takeo, Makoto, Cammer, Michael, Taketo, M. Mark, Gay, Denise L., Millar, Sarah E., Ito, Mayumi

Issue&Volume: 2023-04-19

Abstract: For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations1, which leads to hair greying in most humans and mice2,3. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli4,5,6,7,8. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

DOI: 10.1038/s41586-023-05960-6

Source: https://www.nature.com/articles/s41586-023-05960-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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