French Anna, Yang Cheng-Tao, Taylor Stephen, Watt Suzanne M, Carpenter Lee
1 Stem Cell Research Laboratory, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, and National Health Service Blood and Transplant, University of Oxford , John Radcliffe Hospital, Oxford, United Kingdom .
Stem Cells Dev. 2015 May 1;24(9):1082-95. doi: 10.1089/scd.2014.0318. Epub 2015 Feb 25.
The differentiation of human pluripotent stem cells to the B-cell lymphoid lineage has important clinical applications that include in vitro modeling of developmental lymphogenesis in health and disease. Here, we first demonstrate the capacity of human induced pluripotent stem cells (hiPSCs) to differentiate into CD144(+)CD73(-)CD43/CD235a(-) cells, characterized as hemogenic endothelium, and show that this population is capable of differentiating to CD10(+)CD19(+) B lymphocytes. We also demonstrate that B lymphocytes generated from hiPSCs are able to undergo full VDJ rearrangement and express surface IgM (sIgM(+)), thus representing an immature B-cell subset. Efficiency of sIgM expression on the hiPSC-derived B lymphocytes (∼ 5% of CD19(+) cells) was comparable with B lymphocytes generated from human umbilical cord blood (UCB) hematopoietic progenitor cells. Importantly, when assessed by global transcriptional profiling, hiPSC-derived B-cells show a very high level of similarity when compared with their UCB-derived counterparts, such that from more than 47,000 different transcripts, only 45 were significantly different (with a criteria adjusted P value P<0.05, log FC >1.5 or 2.8-fold). This represents a unique in vitro model to delineate critical events during lymphogeneisis in development and lymphoid diseases such as acute lymphocytic leukemia.
人类多能干细胞向B细胞淋巴谱系的分化具有重要的临床应用价值，包括对健康和疾病状态下发育性淋巴细胞生成进行体外建模。在此，我们首先证明了人类诱导多能干细胞（hiPSC）分化为CD144(+)CD73(-)CD43/CD235a(-)细胞（其特征为造血内皮细胞）的能力，并表明这一细胞群体能够分化为CD10(+)CD19(+) B淋巴细胞。我们还证明，由hiPSC产生的B淋巴细胞能够进行完整的VDJ重排并表达表面IgM（sIgM(+)），因此代表了一个未成熟的B细胞亚群。hiPSC来源的B淋巴细胞上sIgM的表达效率（约占CD19(+)细胞的5%）与源自人脐带血（UCB）造血祖细胞的B淋巴细胞相当。重要的是，通过全基因组转录谱分析评估时，hiPSC来源的B细胞与UCB来源的B细胞相比显示出非常高的相似性，在超过47,000种不同的转录本中，只有45种存在显著差异（标准调整P值P<0.05，log FC >1.5或2.8倍）。这代表了一种独特的体外模型，可用于描绘发育过程中淋巴细胞生成以及诸如急性淋巴细胞白血病等淋巴疾病中的关键事件。
