Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Center for Stem Cell Research, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Stem Cell Reports. 2019 Mar 5;12(3):572-583. doi: 10.1016/j.stemcr.2019.01.006. Epub 2019 Feb 7.
It is generally considered that mouse embryonic stem cell (ESC) differentiation into blood cells in vitro recapitulates yolk sac (YS) hematopoiesis. As such, similar to YS-derived B-progenitors, we demonstrate here that ESC-derived B-progenitors differentiate into B-1 and marginal zone B cells, but not B-2 cells in immunodeficient mice after transplantation. ESC-derived B-1 cells were maintained in the recipients for more than 6 months, secreting natural IgM antibodies in vivo. Gene expression profiling displayed a close relationship between ESC- and YS-derived B-1 progenitors. Because there are no hematopoietic stem cells (HSCs) detectable in our ESC differentiation culture, successful long-term engraftment of ESC-derived functional B-1 cells supports the presence of HSC-independent B-1 cell development.
一般认为,体外培养的小鼠胚胎干细胞(ESC)分化为血细胞可以重现卵黄囊(YS)造血。因此,与 YS 衍生的 B 祖细胞类似,我们在此证明,ESC 衍生的 B 祖细胞在移植到免疫缺陷小鼠后可分化为 B-1 和边缘区 B 细胞,但不能分化为 B-2 细胞。ESC 衍生的 B-1 细胞在受体中维持超过 6 个月,在体内分泌天然 IgM 抗体。基因表达谱显示 ESC 和 YS 衍生的 B-1 祖细胞之间存在密切关系。由于我们的 ESC 分化培养中检测不到造血干细胞(HSCs),因此 ESC 衍生的功能性 B-1 细胞的成功长期植入支持了 HSC 独立的 B-1 细胞发育的存在。