Laboratory of Regenerative Medicine, Center for Preclinical Studies and Technology, Medical University of Warsaw, Ul. Banacha 1B, Warsaw, Poland.
Stem Cell Institute at Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Sci Rep. 2024 Nov 26;14(1):29264. doi: 10.1038/s41598-024-79810-4.
A population of CD133linCD45 and CD34linCD45 very small embryonic-like stem cells (VSELs) has been identified in postnatal human tissues, including bone marrow (BM), mobilized peripheral blood (mPB) and umbilical cord blood (UCB). Under appropriate conditions, VSELs in vitro and in vivo differentiate into tissue-committed stem cells for all three germ layers. Molecular analysis of adult murine BM-purified VSELs revealed that these rare cells deposited during development in adult tissues (i) express a similar transcriptome as embryonic stem cells, (ii) share several markers characteristic for epiblast and migratory primordial germ cells (PGCs), (iii) highly express a polycomb group protein enhancer of zeste drosophila homolog 2 (Ezh2) and finally (iv) display a unique pattern of imprinting at crucial paternally inherited genes that promotes their quiescence. Here, by employing single-cell RNA sequencing we demonstrate for the first time that purified from UCB human VSELs defined by expression of CD34 or CD133 antigens and lack of lineage markers, including CD45 antigen express similar molecular signature as murine BM-derived VSELs. Specifically, unsupervised clustering revealed numerous subpopulations of VSELs including ones i) annotated to germline compartments, ii) regulated by parental imprinting, iii) responding to early developmental fate decisions, iv) transcription factors involved in differentiation and development, including homeobox family of genes, and v) expressing innate immunity and purinergic signaling genes.
已在包括骨髓（BM）、动员外周血（mPB）和脐带血（UCB）在内的出生后人体组织中鉴定出 CD133linCD45 和 CD34linCD45 非常小的胚胎样干细胞（VSELs）群体。在适当的条件下，VSELs 在体外和体内分化为所有三个胚层的组织定向干细胞。对成年鼠 BM 纯化的 VSELs 的分子分析表明，这些在成年组织中发育过程中沉积的稀有细胞（i）表达与胚胎干细胞相似的转录组，（ii）共享几个特征性的内胚层和迁移原始生殖细胞（PGCs）的标志物，（iii）高度表达多梳蛋白组蛋白增强子 drosophila 同源物 2（Ezh2），最后（iv）在关键的父系遗传基因上显示出独特的印迹模式，促进其静止。在这里，我们首次通过单细胞 RNA 测序证明，从 UCB 中纯化的人 VSELs 通过表达 CD34 或 CD133 抗原和缺乏谱系标志物，包括 CD45 抗原，表达与鼠 BM 衍生的 VSELs 相似的分子特征。具体而言，无监督聚类揭示了 VSELs 的许多亚群，包括（i）注释为生殖系区室的亚群，（ii）受亲本印迹调控的亚群，（iii）对早期发育命运决定有反应的亚群，（iv）参与分化和发育的转录因子，包括同源盒基因家族，以及（v）表达先天免疫和嘌呤能信号基因的亚群。
