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Lifelong haematopoiesis is established by hundreds of precursors throughout mammalian ontogeny
Nature Cell Biology ( IF 17.3 ) Pub Date : 2017-09-18 00:00:00 , DOI: 10.1038/ncb3607
Miguel Ganuza , Trent Hall , David Finkelstein , Ashley Chabot , Guolian Kang , Shannon McKinney-Freeman

Current dogma asserts that mammalian lifelong blood production is established by a small number of blood progenitors. However, this model is based on assays that require the disruption, transplantation and/or culture of embryonic tissues. Here, we used the sample-to-sample variance of a multicoloured lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos. We find that approximately 719 Flk1+ mesodermal precursors, 633 VE-cadherin+ endothelial precursors and 545 Vav1+ nascent blood stem and progenitor cells emerge to establish the haematopoietic system at embryonic days (E)7–E8.5, E8.5–E11.5 and E11.5–E14.5, respectively. We also determined that the spatio-temporal recruitment of endothelial blood precursors begins at E8.5 and ends by E10.5, and that many c-Kit+ clusters of newly specified blood progenitors in the aorta are polyclonal in origin. Our work illuminates the dynamics of the developing mammalian blood system during homeostasis.

中文翻译:

终身造血是由整个哺乳动物个体发育中的数百种前体建立的

当前的教条断言,哺乳动物的终身造血是由少数血液祖先建立的。然而,该模型基于需要破坏,移植和/或培养胚胎组织的测定法。在这里,我们使用了多谱系痕迹报告物的样品间差异来评估新兴的终生血液祖细胞的频率,同时避免了胚胎的破坏,培养或移植。我们发现大约719 Flk1 +中胚层前体,633 VE-钙粘着蛋白+内皮前体和545 Vav1 +新生的血液干细胞和祖细胞分别在胚胎第(E)7-E8.5,E8.5-E11.5和E11.5-E14.5时建立了造血系统。我们还确定,内皮血液前体的时空募集始于E8.5,结束于E10.5,并且主动脉中许多新指定的血液祖细胞的c-Kit +簇是起源于多克隆的。我们的工作阐明了动态平衡过程中不断发展的哺乳动物血液系统的动态。
更新日期:2017-09-30
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