Life Sciences Institute, Department of Molecular and Integrative Physiology, University of Michigan Ann Arbor, MI 48109, USA.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02142, USA.
J Cell Sci. 2021 Jul 15;134(14). doi: 10.1242/jcs.258757. Epub 2021 Jul 22.
Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important for maintaining the stem cell population, it is speculated that it underlies tumorigenesis. Therefore, this process must be tightly controlled. Here, we show that a translational regulator, me31B, plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.
组织特异性干细胞通过在生物体的整个生命周期中提供不断分化的细胞供应来维持组织内稳态。分化/正在分化的细胞可以通过去分化回到干细胞状态,以帮助维持个体干细胞寿命之外的干细胞池。尽管去分化对于维持干细胞群体很重要,但据推测它是肿瘤发生的基础。因此,这个过程必须受到严格控制。在这里,我们表明,一种翻译调节剂 me31B 在防止果蝇雄性生殖系中过度去分化中起着关键作用:在没有 me31B 的情况下,精原细胞以显著增加的频率分化为生殖干细胞 (GSC)。我们的结果表明,这种过度去分化可能是由于 nos 的失调,nos 是生殖细胞身份和 GSC 维持的关键调节剂。总之,我们的数据揭示了对去分化的负调控,以平衡干细胞维持与分化。