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Stem Cells International
Volume 2017, Article ID 5762301, 12 pages
https://doi.org/10.1155/2017/5762301
Research Article

Delayed Mesoderm and Erythroid Differentiation of Murine Embryonic Stem Cells in the Absence of the Transcriptional Regulator FUBP1

1Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Strasse 42-44, 60596 Frankfurt/Main, Germany
2LOEWE Center for Cell and Gene Therapy Frankfurt and Department for Medicine, Hematology/Oncology, Goethe University Hospital Frankfurt/Main, 60590 Frankfurt/Main, Germany
3Institute of Biochemistry II, Goethe University Frankfurt, 60590 Frankfurt/Main, Germany
4German Cancer Consortium (DKTK), 69120 Heidelberg, Germany

Correspondence should be addressed to Martin Zörnig; ed.trufknarf-inu.hsg@ginreoz

Received 21 December 2016; Revised 2 March 2017; Accepted 19 March 2017; Published 15 May 2017

Academic Editor: Zhaohui Ye

Copyright © 2017 Josephine Wesely et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The transcriptional regulator far upstream binding protein 1 (FUBP1) is essential for fetal and adult hematopoietic stem cell (HSC) self-renewal, and the constitutive absence of FUBP1 activity during early development leads to embryonic lethality in homozygous mutant mice. To investigate the role of FUBP1 in murine embryonic stem cells (ESCs) and in particular during differentiation into hematopoietic lineages, we generated Fubp1 knockout (KO) ESC clones using CRISPR/Cas9 technology. Although FUBP1 is expressed in undifferentiated ESCs and during spontaneous differentiation following aggregation into embryoid bodies (EBs), absence of FUBP1 did not affect ESC maintenance. Interestingly, we observed a delayed differentiation of FUBP1-deficient ESCs into the mesoderm germ layer, as indicated by impaired expression of several mesoderm markers including Brachyury at an early time point of ESC differentiation upon aggregation to EBs. Coculture experiments with OP9 cells in the presence of erythropoietin revealed a diminished differentiation capacity of Fubp1 KO ESCs into the erythroid lineage. Our data showed that FUBP1 is important for the onset of mesoderm differentiation and maturation of hematopoietic progenitor cells into the erythroid lineage, a finding that is supported by the phenotype of FUBP1-deficient mice.