Qin Jie, Sontag Stephanie, Lin Qiong, Mitzka Saskia, Leisten Isabelle, Schneider Rebekka K, Wang Xiaoying, Jauch Anna, Peitz Michael, Brüstle Oliver, Wagner Wolfgang, Zhao Robert Chunhua, Zenke Martin
1 Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School , Aachen, Germany .
Stem Cells Dev. 2014 Dec 1;23(23):2875-82. doi: 10.1089/scd.2014.0120. Epub 2014 Aug 11.
Human induced pluripotent stem cells (iPS cells) resemble embryonic stem cells and can differentiate into cell derivatives of all three germ layers. However, frequently the differentiation efficiency of iPS cells into some lineages is rather poor. Here, we found that fusion of iPS cells with human hematopoietic stem cells (HSCs) enhances iPS cell differentiation. Such iPS hybrids showed a prominent differentiation bias toward hematopoietic lineages but also toward other mesendodermal lineages. Additionally, during differentiation of iPS hybrids, expression of early mesendodermal markers-Brachyury (T), MIX1 Homeobox-Like Protein 1 (MIXL1), and Goosecoid (GSC)-appeared with faster kinetics than in parental iPS cells. Following iPS hybrid differentiation there was a prominent induction of NODAL and inhibition of NODAL signaling blunted mesendodermal differentiation. This indicates that NODAL signaling is critically involved in mesendodermal bias of iPS hybrid differentiation. In summary, we demonstrate that iPS cell fusion with HSCs prominently enhances iPS cell differentiation.
人诱导多能干细胞（iPS细胞）类似于胚胎干细胞，能够分化为所有三个胚层的细胞衍生物。然而，iPS细胞向某些谱系的分化效率常常相当低。在此，我们发现iPS细胞与人造血干细胞（HSC）融合可增强iPS细胞分化。此类iPS杂种细胞显示出对造血谱系以及其他中胚层和内胚层谱系的显著分化偏向。此外，在iPS杂种细胞分化过程中，早期中胚层和内胚层标志物——短尾型（T）、类MIX1同源盒蛋白1（MIXL1）和类 goosecoid 蛋白（GSC）的表达动力学比亲代iPS细胞更快。iPS杂种细胞分化后，NODAL 显著诱导，而抑制NODAL信号会减弱中胚层和内胚层分化。这表明NODAL信号在iPS杂种细胞分化的中胚层和内胚层偏向中起关键作用。总之，我们证明iPS细胞与HSC融合显著增强了iPS细胞分化。
