Wagh, V., Doss, M. X., Sabour, D., Niemann, R., Meganathan, K., Jagtap, S., Gaspar, J. A., Ardestani, M. A., Papadopoulos, S., Gajewski, M., Winkler, J., Hescheler, J. and Sachinidis, A. (2014). Fam40b is required for lineage commitment of murine embryonic stem cells. Cell Death Dis., 5. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-4889

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Abstract

FAM40B (STRIP2) is a member of the striatin-interacting phosphatase and kinase (STRIPAK) complex that is involved in the regulation of various processes such as cell proliferation and differentiation. Its role for differentiation processes in embryonic stem cells (ESCs) is till now completely unknown. Short hairpin RNA (shRNA)-mediated silencing of Fam40b expression in ESCs and differentiating embryoid bodies (EBs) led to perturbed differentiation to embryonic germ layers and their derivatives including a complete abrogation of cardiomyogenesis. Pluripotency factors such as Nanog, Oct4 and Sox2 as well as epigenetic factors such as histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3-beta (Dnmt3b) were highly upregulated in Fam40b knockdown EBs as compared with control and scrambled EBs. To examine the relevance of Fam40b for development in vivo, Fam40b was knocked down in developing zebrafish. Morpholino-mediated knockdown of Fam40b led to severe abnormalities of the cardiovascular system, including an impaired expression of ventricular myosin heavy chain (vmhc) and of cardiac myosin light chain 2 (cmlc2) in the heart. We identified the gene product of Fam40b in ESCs as a perinuclear and nucleolar protein with a molecular weight of 96 kDa. We conclude that the expression of Fam40b is essential for the lineage commitment of murine embryonic stem cells (mESCs) into differentiated somatic cells via mechanisms involving pluripotency and epigenetic networks.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wagh, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doss, M. X.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabour, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niemann, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meganathan, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jagtap, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaspar, J. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ardestani, M. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papadopoulos, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gajewski, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkler, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sachinidis, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-434277
DOI: 10.1038/cddis.2014.273
Journal or Publication Title: Cell Death Dis.
Volume: 5
Date: 2014
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-4889
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENE-EXPRESSION; NONCODING RNAS; SELF-RENEWAL; MOUSE; DIFFERENTIATION; ZEBRAFISH; GENOME; DNA; METHYLATION; NUCLEOLUSMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43427

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