Mapping mouse hemangioblast maturation from headfold stages.
Mapping mouse hemangioblast maturation from headfold stages.
复制标题
绘制小鼠成血管细胞从头折阶段的成熟情况。
DOI：
10.1016/j.ydbio.2012.02.023
复制
发表时间：
2012
影响因子：
2.7
通讯作者：
Iannaccone,PhilipM
中科院分区：
文献类型：
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作者：
Rhee,JerryM;Iannaccone,PhilipM
在神经板/头褶阶段（NP/HF，~7.5dpc-8dpc）的小鼠后原条代表了可以分离成血管细胞的最佳窗口。我们使用已建立的单克隆抗体对影响血液和内皮命运的蛋白质进行免疫组织化学。我们证明，HoxB 4和GATA 1是第一组标记物，分离独立的内皮细胞或血液种群在NP/HF阶段的小鼠胚胎发育。在一个细胞子集中，两种蛋白质共表达，并且免疫反应性在核空间内似乎相互排斥。我们在造血干细胞出现的后期部位寻找这种特殊状态，即，在10.5-11.5dpc的AGM和胎肝中，发现只有极少数细胞具有这种特征。基于这一时空的论点，我们提出，最早的血液祖细胞出现直接从外胚层或通过分离内的尿囊核心域（ACD）通过减少细胞粘附和pSmad 1/5核信号，随后由一个随机的决定对血液或内皮细胞的命运，涉及GATA 1和HoxB 4，分别。结合分布平衡的第三种形式可能代表成血管细胞和HSC共有的共同条件。我们开发了一个启发式的成血管细胞成熟模型，部分是为了明确我们的假设。
The mouse posterior primitive streak at neural plate/headfold stages (NP/HF, ~7.5dpc–8dpc) represents an optimal window from which hemangioblasts can be isolated. We performed immunohistochemistry on this domain using established monoclonal antibodies for proteins that affect blood and endothelial fates. We demonstrate that HoxB4 and GATA1 are the first set of markers that segregate independently to endothelial or blood populations during NP/HF stages of mouse embryonic development. In a subset of cells, both proteins are co-expressed and immunoreactivities appear mutually excluded within nuclear spaces. We searched for this particular state at later sites of hematopoietic stem cell emergence, viz., the aorta–gonad–mesonephros (AGM) and the fetal liver at 10.5–11.5dpc, and found that only a rare number of cells displayed this character. Based on this spatial–temporal argument, we propose that the earliest blood progenitors emerge either directly from the epiblast or through segregation within the allantoic core domain (ACD) through reduction of cell adhesion and pSmad1/5 nuclear signaling, followed by a stochastic decision toward a blood or endothelial fate that involves GATA1 and HoxB4, respectively. A third form in which binding distributions are balanced may represent a common condition shared by hemangioblasts and HSCs. We developed a heuristic model of hemangioblast maturation, in part, to be explicit about our assumptions.