title: 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.
authors.affiliation: 1 Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School , Aachen, Germany .
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sontag
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.forename: Saskia
authors.initials: S
authors.lastname: Mitzka
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leisten
authors.forename: Rebekka K
authors.initials: RK
authors.lastname: Schneider
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Michael
authors.initials: M
authors.lastname: Peitz
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation; D002459:Cell Fusion; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation