Tracing the origin of the HSC hierarchy reveals an SCF-dependent, IL-3-independent CD43(-) embryonic precursor.
Tracing the origin of the HSC hierarchy reveals an SCF-dependent, IL-3-independent CD43(-) embryonic precursor.
复制标题
DOI：
10.1016/j.stemcr.2014.07.009
复制
发表时间：
2014-09-09
影响因子：
5.9
通讯作者：
Medvinsky, Alexander
中科院分区：
文献类型：
--
作者：
Rybtsov, Stanislav;Batsivari, Antoniana;Bilotkach, Kateryna;Paruzina, Daria;Senserrich, Jordi;Nerushev, Oleg;Medvinsky, Alexander
造血干细胞（HSCs）在主动脉、性腺、中肾（AGM）区域以逐步方式发育。I型前-HSC表达CD 41但缺乏CD 45表达，其随后在II型前-HSC中在其成熟为永久性HSC之前上调。在这里，使用离体模型的HSC发展，我们确定了永久性HSC的前体干的胚胎第9.5天（E9.5）的小鼠胚胎。这些前体，在此称为原HSC，比I型和II型前HSC更不成熟。虽然原HSC是CD 41+，但它们缺乏CD 43标记，其在发育中的HSC谱系中逐渐上调。我们发现，干细胞因子（SCF），而不是白细胞介素-3（IL-3），是一个主要的效应，在E9-E10的HSC成熟。这项研究进一步扩展了先前建立的发展中HSC谱系的层次组织，并将其作为一个差异调节的四步过程，并确定了其他靶点，这些靶点可以促进从多能细胞中产生可移植的HSC，以满足临床需求。Pro-HSC是E9.5背主动脉中终末HSC的早期胚胎前体细胞。与CFU-C相比，pro-HSC缺乏CD 43标记，cKIT表达低，SCF而不是IL-3促进pro-HSC向终末HSC的进展。Medvinsky及其同事表明，E9.5小鼠胚胎含有定形造血干细胞（HSCs）的前体细胞，这些细胞与后期发育阶段的细胞是可以区分的。这种CD 41+前体，在此称为“pro-HSC”，不表达CD 43标志物，其在发育后期被上调。Pro-HSC可以响应于SCF而成熟为永久性HSC，但不响应于IL-3。
Definitive hematopoietic stem cells (HSCs) develop in the aorta gonad mesonephros (AGM) region in a stepwise manner. Type I pre-HSCs express CD41 but lack CD45 expression, which is subsequently upregulated in type II pre-HSCs prior to their maturation into definitive HSCs. Here, using ex vivo modeling of HSC development, we identify precursors of definitive HSCs in the trunk of the embryonic day 9.5 (E9.5) mouse embryo. These precursors, termed here pro-HSCs, are less mature than type I and II pre-HSCs. Although pro-HSCs are CD41+, they lack the CD43 marker, which is gradually upregulated in the developing HSC lineage. We show that stem cell factor (SCF), but not interleukin-3 (IL-3), is a major effector of HSC maturation during E9–E10. This study extends further the previously established hierarchical organization of the developing HSC lineage and presents it as a differentially regulated four-step process and identifies additional targets that could facilitate the generation of transplantable HSCs from pluripotent cells for clinical needs. Pro-HSCs are early embryonic precursors of definitive HSCs in E9.5 dorsal aorta In contrast to CFU-C, pro-HSCs lack CD43 marker and have low cKIT expression SCF, but not IL-3, promotes progression of pro-HSCs into definitive HSCs HSCs develop hierarchically in a four-step process In this article, Medvinsky and colleagues show that the E9.5 mouse embryo contains precursors of definitive hematopoietic stem cells (HSCs) that are distinguishable from those at later developmental stages. This CD41+ precursor, termed here “pro-HSC,” does not express CD43 marker, which is upregulated later on in development. Pro-HSCs can mature into definitive HSCs in response to SCF, but not to IL-3.
登录
查看更多内容
DOI：
10.1084/jem.20120993
发表时间：
2013-01-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guiu J;Shimizu R;D'Altri T;Fraser ST;Hatakeyama J;Bresnick EH;Kageyama R;Dzierzak E;Yamamoto M;Espinosa L;Bigas A
通讯作者：
Bigas A
影响因子：
20.3
作者：
Mikkola, HKA;Fujiwara, Y;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
20.3
作者：
McKinney-Freeman, Shannon L.;Naveiras, Olaia;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
64.8
作者：
MANJUNATH, N;CORREA, M;ARDMAN, B
通讯作者：
ARDMAN, B
影响因子：
32.4
作者：
Drew, E;Merzaban, JS;McNagny, KM
通讯作者：
McNagny, KM