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[小鼠胚胎内造血]

[Intra-embryonic hematopoiesis in mice].

作者信息

Cumano A, Garcia-Porrero J, Dieterlen-Lievre F, Godin I

机构信息

Unité de Biologie Moléculaire du Gène, Institut Pasteur, Paris, France.

出版信息

C R Seances Soc Biol Fil. 1995;189(4):617-27.

PMID:8564576
Abstract

In vertebrate embryos, all hemopoietic tissues that are successively active during ontogeny (fetal liver, thymus, spleen and bone marrow) are colonized by extrinsic hemopoietic stem cells (HSC). The exception to this rule is the yolk sac (YS) whose progenitors arise in situ. Moreover, the YS is the first hemopoietic site to appear in the embryo. In consequence, it was considered as the primary source of the HSC that transfer from one site to the other until the demonstration that, in birds, the source of definitive HSC was located in the aortic region of the embryo. To assess a possible contribution of intraembryonic sites to mouse hemopoietic development, we developed an in vitro approach that permits the detection of multipotent hemopoietic progenitors in the region surrounding the dorsal aorta. This new site, the paraaortic splanchnopleura (P-Sp), is active from the 10 somite stage to the stage of fetal liver colonization by HSC. The in vitro analysis of the hemopoietic potential of the P-Sp revealed that: 1) progenitors present in this region are multipotent since a single micromanipulated P-Sp cell can give rise to mature B and T lymphocytes and various myeloid cells, when cultivated in appropriate conditions; 2) the P-Sp is the only intraembryonic site endowed with this potential; 3) numbering progenitors present in the YS and P-Sp indicated that precursors appear in both locations at the 10-12 somite stage reaching 15 in each site at 9.5 dpc (25 somites), shortly before the beginning of fetal liver colonisation. During a cytological study of the 9-11 dpc embryo aimed to disclose the cellular basis for our experimental results, two potential hemopoietic sites were uncovered. Cells clusters that resemble avian intraaortic hemopoietic clusters were found in the arteries located close to the coelomic cavity (dorsal aorta, umbilical and omphalomesenteric arteries). Moreover, groups of cells strikingly similar to YS blood islands were uncovered in the mesentery. All these sites are located in areas formed from the P-Sp and are fully developed at the onset of fetal liver colonization. These hemogenic sites most probably develop from the hemopoietic precursors present in the P-Sp.

摘要

在脊椎动物胚胎中,个体发育过程中相继活跃的所有造血组织(胎儿肝脏、胸腺、脾脏和骨髓)均由外源性造血干细胞(HSC)定植。该规则的例外是卵黄囊(YS),其祖细胞在原位产生。此外,卵黄囊是胚胎中最早出现的造血部位。因此,它被认为是造血干细胞的主要来源,这些造血干细胞从一个部位转移到另一个部位,直到有证据表明,在鸟类中,定型造血干细胞的来源位于胚胎的主动脉区域。为了评估胚胎内部位对小鼠造血发育的可能贡献,我们开发了一种体外方法,该方法可以检测背主动脉周围区域的多能造血祖细胞。这个新部位,即主动脉旁脏壁层(P-Sp),从10体节期到造血干细胞定植胎儿肝脏的阶段都处于活跃状态。对P-Sp造血潜能的体外分析表明:1)该区域存在的祖细胞具有多能性,因为单个经显微操作的P-Sp细胞在适当条件下培养时可产生成熟的B和T淋巴细胞以及各种髓系细胞;2)P-Sp是唯一具有这种潜能的胚胎内部位;3)对卵黄囊和P-Sp中存在的祖细胞进行计数表明,前体细胞在10-12体节期出现在这两个部位,在妊娠第9.5天(25体节)时每个部位达到15个,就在胎儿肝脏定植开始前不久。在对妊娠第9-11天胚胎进行细胞学研究以揭示我们实验结果的细胞基础时,发现了两个潜在的造血部位。在靠近体腔的动脉(背主动脉、脐动脉和卵黄肠动脉)中发现了类似于鸟类主动脉内造血簇的细胞簇。此外,在肠系膜中发现了与卵黄囊血岛极为相似的细胞群。所有这些部位都位于由P-Sp形成的区域,并且在胎儿肝脏定植开始时就已完全发育。这些造血部位很可能由P-Sp中存在的造血前体细胞发育而来。

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