Molecular signature of adult bone marrow-purified very small embryonic-like stem cells supports their developmental epiblast/germ line origin
Molecular signature of adult bone marrow-purified very small embryonic-like stem cells supports their developmental epiblast/germ line origin
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DOI：
10.1038/leu.2010.121
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发表时间：
2010-08-01
期刊：
影响因子：
11.4
通讯作者：
Ratajczak, M. Z.
中科院分区：
文献类型：
--
作者：
Shin, D-M;Liu, R.;Ratajczak, M. Z.
我们推测从成人骨髓中分离的Oct4(+)SSEA-1(+)SCA-1(+)Lin(-)CD45(-)极小胚胎样干细胞(VSEL)可能是组织定向干细胞的储备群体。本研究的目的是阐明这些细胞的发育起源。我们报道，在胚胎发育过程中，VSEL在胚胎12.5天的小鼠胎肝(FLS)中丰富，随后沿着造血干细胞(H)SCs的发育路线在BM上定植。对纯化的VSEL的分子分析表明，FL来源的VSEL和它们的成年BM来源的VSEL都表达：(I)几个上胚层/原始生殖细胞(PGC)标记；(Ii)Oct4、Nanog和Stella基因座的迁移PGC样重编程特征；以及(Iii)独特的基因组印记模式。因此，这些数据表明，VSEL可能起源于上皮样细胞/迁移的PGC样细胞，尽管表达了多潜能干细胞标记，但印记基因的表观遗传特征的变化使这些细胞在成人组织中保持静止，并防止它们形成畸胎瘤。白血病(2010年)24,1450-1461；doi：10.1038/leu 2010.121；2010年5月27日在线发布
We postulated that Oct4(+)SSEA-1(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs) isolated from adult bone marrow (BM) could be a reserve population for tissue-committed stem cells. The aim of this study was to elucidate the developmental origin of these cells. We report that during embryogenesis, VSELs are enriched in embryonic day (E)12.5 murine fetal livers (FLs) and subsequently follow the developmental route of hematopoietic stem cells (H) SCs to colonize BM. Molecular analysis of purified VSELs revealed that both FL-derived VSELs and their adult BM-derived counterparts express: (i) several epiblast/primordial germ cell (PGC) markers; (ii) migrating PGC-like epigenetic reprogramming profiles of Oct4, Nanog and Stella loci; as well as (iii) a unique pattern of genomic imprinting. Thus, these data suggest that VSELs may originate from epiblast/migrating PGC-like cells and, in spite of the expression of pluripotent stem cell markers, changes in the epigenetic signature of imprinted genes keep these cells quiescent in adult tissues and prevent them from teratoma formation. Leukemia (2010) 24, 1450-1461; doi:10.1038/leu.2010.121; published online 27 May 2010