Molecular signature of adult bone marrow-purified very small embryonic-like stem cells supports their developmental epiblast/germ line origin

被引：76
作者：
Shin, D-M [1 ]
Liu, R. [1 ]
Klich, I. [1 ]
Wu, W. [1 ]
Ratajczak, J. [1 ]
Kucia, M. [1 ]
Ratajczak, M. Z. [1 ]
机构：
[1] Univ Louisville, James Graham Brown Canc Ctr, Stem Cell Inst, Louisville, KY 40202 USA
来源：
LEUKEMIA | 2010年 / 24卷 / 08期
关键词：
VSELs; epiblast; PGCs; CXCR4; epigenetics; PRIMORDIAL GERM-CELLS; HEMATOPOIETIC SYSTEM; MOUSE EMBRYO; SPECIFICATION; METHYLATION; DYNAMICS; GENES; HETEROGENEITY; ESTABLISHMENT; MECHANISMS;
D O I：
10.1038/leu.2010.121
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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
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页码：1450 / 1461
页数：12
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