Early Development of Definitive Erythroblasts from Human Pluripotent Stem Cells Defined by Expression of Glycophorin A/CD235a, CD34, and CD36
Early Development of Definitive Erythroblasts from Human Pluripotent Stem Cells Defined by Expression of Glycophorin A/CD235a, CD34, and CD36
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由血型糖蛋白 A/CD235a、CD34 和 CD36 的表达定义的人多能干细胞的成红细胞的早期发育
作者：
Bin Mao;Shu Huang;Xulin Lu;Wencui Sun;Ya Zhou;Xu Pan;Jinfeng Yu;Mowen Lai;Bo Chen;Qiongxiu Zhou;Song Mao;Guohui Bian;Jiaxi Zhou;Tatsutoshi Nakahata;Feng Ma
人红系细胞的发育主要是在成人造血模型中研究的，而其在胚胎和胎儿阶段的早期起源在很大程度上是未知的。我们用一种有效的fi共培养系统观察了人多能干细胞(HPSCs)来源的红系细胞的发育和成熟。这些来源于hPSC的早期红细胞最初表现出Defi原性特征，具有血糖素A+的特征。CD34低CD36表型，不同于成人CD34+细胞来源的CD34+CD36。在失去CD34表达后，早期GPA+CD36红细胞成熟到GPA+CD36低/+阶段，因为后者表达更高水平的b-珠蛋白。伴随着中胚层和内皮特性的逐渐丧失，并最终抑制CD36。我们建立了一个独特的体外模型，通过连续表达CD34、GPA和CD36来追踪hPSC来源的红细胞的早期发育。我们的findings可能为深入了解人类早期红细胞生成以及最终的治疗潜力提供帮助。
The development of human erythroid cells has beenmostly examined inmodels of adult hematopoiesis,while their early derivation dur-.ing embryonic and fetal stages is largely unknown.We observed the development andmaturation of erythroblasts derived fromhuman.pluripotent stemcells (hPSCs) by an efficient co-culture system. These hPSC-derived early erythroblasts initially showed definitive char-.acteristics with a glycophorin A+.(GPA+.) CD34lowCD36 phenotype and were distinct from adult CD34+.cell-derived ones. After losing.CD34 expression, early GPA+.CD36 erythroblasts matured into GPA+.CD36low/+.stage as the latter expressed higher levels of b-globin.along with a gradual loss of mesodermal and endothelial properties, and terminally suppressed CD36. We establish a unique in vitro.model to trace the early development of hPSC-derived erythroblasts by serial expression of CD34, GPA, and CD36.Our findingsmay pro-.vide insight into the understanding of human early erythropoiesis and, ultimately, therapeutic potential.