Epiblast-derived stem cells in embryonic and adult tissues
Epiblast-derived stem cells in embryonic and adult tissues
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DOI：
10.1387/ijdb.072413md
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发表时间：
2009-01-01
影响因子：
0.7
通讯作者：
Nistal, Manuel
中科院分区：
文献类型：
--
作者：
De-Miguel, Maria P.;Arnalich-Montiel, Francisco;Nistal, Manuel
多能细胞可以在胚泡阶段从胚胎的哺乳动物内细胞团(ICM)中分离出来，并在培养中保持为未分化的胚胎干细胞(ES)。这些细胞是哺乳动物体外发育的重要模型，也是它们在细胞治疗中应用的大量研究的焦点。在体内，在胚泡阶段后不久，ICM分离成两层：形成卵黄囊的次母细胞和外胚层。上胚层干细胞和ES细胞一样，是多能的。上胚层很早就分化为生殖细胞前体细胞，即原始生殖细胞(PGC)。PGCs可以产生胚胎癌细胞，这是睾丸肿瘤的多能干细胞。在正常胚胎发育期间，PGCs迁移到主动脉-性腺-中肾区域(AGM)。有趣的是，这一地区也是第一波胚胎造血的港湾。随后的造血波涉及AGM-造血干细胞(HSC)在胎儿肝脏、胸腺、脾的定植，并最终在成人造血的骨髓(BM)定植。骨髓也是间充质干细胞(MSCs)的来源。AGM区细胞分化为间皮细胞，是骨髓HSC和MSC的胚胎前体细胞。最近对成体骨髓中具有典型PGC标志的细胞亚群的鉴定表明，HSCs起源于一种共同的PGC前体细胞和来源于外胚层的HSCs。几个小组已经描述了在表皮、支气管上皮、胰腺、视网膜、毛囊、心脏和牙髓等器官中存在具有相同标记的干细胞。这种存在支持了这样的假设，即在早期发育过程中，外胚层/生殖系来源的细胞沉积在各种器官中，并持续到成年期。问题在于，这些多能干细胞是否只是发育中的残留物，或者它们是否不断地促进组织的更新，从而可以重新激活以用于组织再生，而不需要干细胞移植来进行人类细胞治疗。
Pluripotent cells can be isolated from the mammalian inner cell mass (ICM) of the embryo at the blastocyst stage, and maintained in culture as undifferentiated, embryonic stem cells (ES). These cells are an important model of mammalian development in vitro and are the focus of a great deal of research for their use in Cell Therapy. In vivo, shortly after the blastocyst stage, the ICM segregates into two layers: the hypoblast which will give rise to the yolk sac, and the epiblast. Epiblast stem cells, like ES cells, are pluripotent. The epiblast will differentiate very early into germ cell progenitors, the primordial germ cells (PGC). PGCs can give rise to embryonal carcinoma cells, the pluripotent stem cells of testicular tumors. During normal embryo development, PGCs migrate into the aorta-gonad-mesonephros region (AGM). Interestingly, this region also harbors the first wave of embryonic hematopoiesis. Subsequent waves of hematopoiesis involve AGM-hematopoietic stem cell (HSC) colonization of the fetal liver, thymus, spleen and ultimately, for adult hematopoiesis,the bone marrow (BM). The BM is also source of mesenchymal stem cells (MSCs). It is accepted that the AGM region cells give rise to the mesothelial cells which are the embryonic precursors of the HSC and MSC of the BM. Recent identification of a subpopulation of cells with markers typical of PGCs in the adult BM, which are capable of differentiating into HSCs, suggests that HSCs originate from a common precursor of PGCs and HSCs derived from the epiblast. Several groups have described the presence of stem cells with the same markers in epidermis, bronchial epithelium, pancreas, retina, hair follicle, heart and dental pulp among, other organs. This presence supports the hypothesis that during early development, epiblast/germ line-derived cells are deposited in various organs which persist into adulthood. The question remains whether these pluripotent stem cells are only developmental remnants or if they continuously contribute to the renewal of tissues, and thus can be reactivated for tissue regeneration without the need for stem cell transplantation for human cell therapies.