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Cell fusion enhances mesendodermal differentiation of human induced pluripotent stem cells.


ABSTRACT: 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.

SUBMITTER: Qin J 

PROVIDER: S-EPMC4235980 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Cell fusion enhances mesendodermal differentiation of human induced pluripotent stem cells.

Qin Jie J   Sontag Stephanie S   Lin Qiong Q   Mitzka Saskia S   Leisten Isabelle I   Schneider Rebekka K RK   Wang Xiaoying X   Jauch Anna A   Peitz Michael M   Brüstle Oliver O   Wagner Wolfgang W   Zhao Robert Chunhua RC   Zenke Martin M  

Stem cells and development 20140811 23


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. A  ...[more]

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