Delayed mesoderm and erythroid differentiation of murine embryonic stem cells in the absence of the transcriptional regulator FUBP1

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 le
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.
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Metadaten
Author:Josephine Wesely, Marlene Steiner, Frank Schnütgen, Manuel Kaulich, Michael A. Rieger, Martin Zörnig
URN:urn:nbn:de:hebis:30:3-506526
DOI:http://dx.doi.org/10.1155/2017/5762301
ISSN:1687-9678
ISSN:1687-966X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28588622
Parent Title (English):Stem cells international
Publisher:Sage-Hindawi
Place of publication:London [u. a.]
Contributor(s):Zhaohui Ye
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/05/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/08/12
Volume:2017
Issue:Art. 5762301
Pagenumber:13
First Page:1
Last Page:12
Note:
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.
HeBIS PPN:453936911
Institutes:Biochemie und Chemie
Medizin
Georg-Speyer-Haus
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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