美国哈佛大学Mansi Srivastava小组揭示成体多能干细胞的胚胎起源。相关论文发表在2022年12月8日出版的《细胞》杂志上。

研究人员利用了Hofstenia miamia（一种再生蠕虫），它拥有集体多能的成体多能干细胞（aPSC），称为neoblast，并产生可操纵的胚胎。系谱追踪和功能实验显示，一对胚胎产生的细胞在分布、行为和基因表达方面类似于新细胞。在Hofstenia中，aPSC包括转录不同的亚群，表达与分化组织相关的标记；数据表明，尽管它们具有异质性，aPSC在发育过程中来自一个谱系，而不是来自多个组织特异性谱系。

接下来，研究人员将整个发育过程中的单细胞转录组分析与新成体细胞系追踪结合起来，确定了新成体形成的分子轨迹，包括转录因子Hes、FoxO和Tbx。这种对aPSC形成的细胞机制和分子轨迹的鉴定为aPSC的体内调节和演化研究打开了大门。

据了解，虽然在许多动物谱系中发现了aPSC，但它们在胚胎发育过程中的形成机制尚不清楚。

附：英文原文

Title: Embryonic origins of adult pluripotent stem cells

Author: Julian O. Kimura, D. Marcela Bolaos, Lorenzo Ricci, Mansi Srivastava

Issue&Volume: 2022/12/08

Abstract: Although adult pluripotent stem cells (aPSCs) are found in many animal lineages, mechanismsfor their formation during embryogenesis are unknown. Here, we leveraged Hofstenia miamia, a regenerative worm that possesses collectively pluripotent aPSCs called neoblastsand produces manipulable embryos. Lineage tracing and functional experiments revealedthat one pair of blastomeres gives rise to cells that resemble neoblasts in distribution,behavior, and gene expression. In Hofstenia, aPSCs include transcriptionally distinct subpopulations that express markers associatedwith differentiated tissues; our data suggest that despite their heterogeneity, aPSCsare derived from one lineage, not from multiple tissue-specific lineages during development.Next, we combined single-cell transcriptome profiling across development with neoblastcell-lineage tracing and identified a molecular trajectory for neoblast formationthat includes transcription factors Hes, FoxO, and Tbx. This identification of a cellularmechanism and molecular trajectory for aPSC formation opens the door for in vivo studies of aPSC regulation and evolution.

DOI: 10.1016/j.cell.2022.11.008

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01420-9