Molecular characterization of isolated from murine adult tissues very small embryonic/epiblast like stem cells (VSELs).
Molecular characterization of isolated from murine adult tissues very small embryonic/epiblast like stem cells (VSELs).
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从小鼠成体组织中分离出的非常小的胚胎/外胚层样干细胞 (VSEL) 的分子特征。
DOI：
10.1007/s10059-010-0081-4
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发表时间：
2010
影响因子：
3.8
通讯作者：
Ratajczak,MariuszZ
中科院分区：
文献类型：
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作者：
Shin,Dong-Myung;Liu,Rui;Klich,Izabela;Ratajczak,Janina;Kucia,Magda;Ratajczak,MariuszZ
多能的非常小的胚胎/上胚层来源的干细胞（VSEL），如我们假设的，在原肠胚形成的开始沉积在发育中的组织中，并且作为组织定向干细胞（TCSC）的多能干细胞（PSC）的后备群体发挥重要作用。我们设想，在稳态条件下，这些细胞可能参与组织再生和器官损伤后的再生/修复过程。成人骨髓（BM）衍生的纯化VSEL的分子分析揭示它们i）表达多能干细胞标志物，Oct 4、Nanog、Klf-4、SSEA-1 ii）共享几种外胚层以及迁移性原始生殖细胞（PGCs）的特征性标记，和iii）具有独特的基因组印记模式（例如，Igf 2-H19和Rasgrf 1基因座上不同甲基化区域的缺失以及KCNQ 1和Igf 2 R基因座上的超甲基化）。这支持了VSEL与外胚层来源的迁移性PGC样细胞相关，尽管它们具有多能干细胞特性，但印迹基因的表观遗传特征的变化使这些细胞在成体组织中保持静止，并防止它们形成畸胎瘤。相反，导致印记基因激活的表观遗传变化/突变可能导致这些细胞形成肿瘤。越来越多的证据表明，印迹基因表达的扰动是肿瘤发展中观察到的一种常见现象。
Pluripotent very small embryonic/epiblast derived stem cells (VSELs) as we hypothesize are deposited at begin of gastrulation in developing tissues and play an important role as backup population of pluripotent stem cells (PSCs) for tissue committed stem cells (TCSCs). We envision that during steady state conditions these cells may be involved in tissue rejuvenation and in processes of regeneration/repair after organ injuries. Molecular analysis of adult bone marrow (BM)-derived purified VSELs revealed that they i) express pluripotent stem cells markers e.g., Oct4, Nanog, Klf-4, SSEA-1 ii) share several markers characteristic for epiblast as well as migratory primordial germ cells (PGCs), and iii) possess a unique pattern of genomic imprinting (e.g., erasure of differently methylated regions at Igf2-H19 and Rasgrf1 loci and hypermethylation at KCNQ1 and Igf2R loci). This supports that VSELs are related to epiblast-derived migrating PGC-like cells and, despite their pluripotent stem cell character, changes in the epigenetic signature of imprinted genes keep these cells quiescent in adult tissues and prevent them from teratoma formation. In contrast epigenetic changes/mutations that lead to activation of imprinted genes could potentially lead to tumor formation by these cells. Mounting evidence accumulates that perturbation of expression of imprinted genes is a common phenomenon observed in developing tumors.