Maturation of hematopoietic stem cells from prehematopoietic stem cells is accompanied by up-regulation of PD-L1.
Maturation of hematopoietic stem cells from prehematopoietic stem cells is accompanied by up-regulation of PD-L1.
复制标题
DOI：
10.1084/jem.20161594
复制
发表时间：
2018-02-05
期刊：
影响因子：
--
通讯作者：
Speck NA
中科院分区：
文献类型：
--
作者：
Tober J;Maijenburg MMW;Li Y;Gao L;Hadland BK;Gao P;Minoura K;Bernstein ID;Tan K;Speck NA
Tober等人的研究表明，与体外相比，在胎儿肝脏中从造血干细胞前成熟的造血干细胞（hsc）在分子上并不等同。虽然两者都表达细胞表面程序性死亡配体1 (PD-L1)，但胚胎造血干细胞移植到成人受体中并不需要PD-L1。造血干细胞（hsc）由起源于胚胎大动脉的造血干细胞前发育成熟。为了从体外来源鉴定造血干细胞，有必要完善体外成熟造血干细胞的标记物。我们纯化并比较了预造血干细胞、离体成熟造血干细胞和胎儿肝造血干细胞的转录组。我们发现造血干细胞在体内或离体成熟过程中都伴随着与胚胎发育和血管发生相关基因的下调，以及与造血器官发育、淋巴细胞发育和免疫应答相关基因的上调。离体成熟的造血干细胞比前造血干细胞更接近于胎儿肝造血干细胞，但不是它们的分子等效物。我们发现离体成熟和胎肝hsc表达程序性死亡配体1 （PD-L1）。PD-L1并不标记所有的造血干细胞，但细胞表面PD-L1存在于体外成熟的造血干细胞上。胚胎造血干细胞的移植不需要PD-L1信号。因此，PD-L1的上调与HSC成熟相关，但不是必需的。
Tober et al. show that hematopoietic stem cells (HSCs) that mature from pre-HSCs in vivo in the fetal liver, versus ex vivo, are not molecularly equivalent. Although both express cell surface programmed death ligand 1 (PD-L1), it is not required for the engraftment of fetal HSCs into adult recipients. Hematopoietic stem cells (HSCs) mature from pre-HSCs that originate in the major arteries of the embryo. To identify HSCs from in vitro sources, it will be necessary to refine markers of HSCs matured ex vivo. We purified and compared the transcriptomes of pre-HSCs, HSCs matured ex vivo, and fetal liver HSCs. We found that HSC maturation in vivo or ex vivo is accompanied by the down-regulation of genes involved in embryonic development and vasculogenesis, and up-regulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. Ex vivo matured HSCs more closely resemble fetal liver HSCs than pre-HSCs, but are not their molecular equivalents. We show that ex vivo–matured and fetal liver HSCs express programmed death ligand 1 (PD-L1). PD-L1 does not mark all pre-HSCs, but cell surface PD-L1 was present on HSCs matured ex vivo. PD-L1 signaling is not required for engraftment of embryonic HSCs. Hence, up-regulation of PD-L1 is a correlate of, but not a requirement for, HSC maturation.
登录
查看更多内容
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
3.5
作者：
Lee, SJ;Jang, BC;Choi, IH
通讯作者：
Choi, IH
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y