Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver.
Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver.
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DOI：
10.1242/dev.131193
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发表时间：
2016-04-15
期刊：
影响因子：
--
通讯作者：
Medvinsky A
中科院分区：
文献类型：
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作者：
Rybtsov S;Ivanovs A;Zhao S;Medvinsky A
在E12.5的胎儿肝脏中大量出现造血干细胞（HSC）的前一天，胚胎仅含有少量永久性HSC。据认为，胎儿肝脏中HSC活性的爆发是由永久性HSC的未成熟胚胎前体（称为前HSC）的快速成熟所支撑的。然而，由于前HSC不能通过直接移植到成年辐射受体中来检测，因此代表成人造血系统胚胎雏形的该群体的大小和生长仍然不确定。使用一种新的定量分析，我们证明，从E9.5的前HSC池经历了显着的增长，在性腺-中肾区域，并通过E11.5达到的大小，在E12.5胎儿肝脏中的永久性HSC的数量相匹配。因此，这项研究首次为我们理解大量的确定性HSC如何在胎儿肝脏中出现提供了定量基础。总结：定量方法揭示了前HSC池如何在AGM区域经历急剧增长，并且在E11.5达到与E12.5胎儿肝脏中的永久HSC数量相匹配的大小。
One day prior to mass emergence of haematopoietic stem cells (HSCs) in the foetal liver at E12.5, the embryo contains only a few definitive HSCs. It is thought that the burst of HSC activity in the foetal liver is underpinned by rapid maturation of immature embryonic precursors of definitive HSCs, termed pre-HSCs. However, because pre-HSCs are not detectable by direct transplantations into adult irradiated recipients, the size and growth of this population, which represents the embryonic rudiment of the adult haematopoietic system, remains uncertain. Using a novel quantitative assay, we demonstrate that from E9.5 the pre-HSC pool undergoes dramatic growth in the aorta-gonad-mesonephros region and by E11.5 reaches the size that matches the number of definitive HSCs in the E12.5 foetal liver. Thus, this study provides for the first time a quantitative basis for our understanding of how the large population of definitive HSCs emerges in the foetal liver. Summary: A quantitative approach reveals how the pre-HSC pool undergoes dramatic growth in the AGM region and, by E11.5, reaches the size that matches the number of definitive HSCs in the E12.5 foetal liver.