从人脐带中分离的 Muse 细胞具有人类着床后胚泡样特征。
Human post-implantation blastocyst-like characteristics of Muse cells isolated from human umbilical cord.
机构信息
Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan.
Department of Public Health, Kobe University Graduate School of Health Science, Kobe, Japan.
出版信息
Cell Mol Life Sci. 2024 Jul 11;81(1):297. doi: 10.1007/s00018-024-05339-4.
Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine.
Muse 细胞被鉴定为多能表面标志物 SSEA-3 阳性细胞,是位于骨髓(BM)、外周血和器官结缔组织中的多能内源性干细胞。然而,胚胎外组织中 SSEA-3(+)细胞的详细特征尚不清楚。在这里,我们证明了类似于从 BM、脂肪组织和真皮中收集的人成体组织-Muse 细胞,人脐带(UC)-SSEA-3(+)细胞表达多能性标志物,在单细胞水平上分化为三胚层谱系细胞,迁移到受损组织,并表现出低端粒酶活性和非致瘤性。值得注意的是,~20%的人 UC-SSEA-3(+)细胞为 X 失活特异性转录物(XIST)阴性,这是一种原始多能干细胞特征,而所有的人成体组织-Muse 细胞均为 XIST 阳性。单细胞 RNA 测序显示,人 UC-SSEA-3(+)细胞的基因表达谱与人类着床后胚泡更为相似,而与人成体组织-Muse 细胞相似。DNA 甲基化水平也呈现出相同的趋势,值得注意的是,人 UC-SSEA-3(+)细胞中与分化特别相关的基因的甲基化水平低于人成体组织-Muse 细胞。此外,人 UC-SSEA-3(+)细胞在体外诱导分化后新表达胚外、生殖系和造血谱系特异性标志物,而人成体组织-Muse 细胞仅部分响应诱导。在活体中的各种干细胞/祖细胞中,尚未在人类中发现类似于原始着床后胚泡的具有类似特性的细胞。易于获得的人 UC-SSEA-3(+)细胞可能是研究人类早期发育和人类生殖医学的有价值的工具。