title: Fam40b is required for lineage commitment of murine embryonic stem cells.
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-β (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.
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Wagh
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: M X
authors.initials: MX
authors.lastname: Doss
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Sabour
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Niemann
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Meganathan
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jagtap
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: J A
authors.initials: JA
authors.lastname: Gaspar
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Ardestani
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Papadopoulos
authors.affiliation: Institute for Genetics, University of Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gajewski
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Winkler
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Sachinidis
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D058732:Embryoid Bodies / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D051379:Mice
chemical_list: D018797:Cell Cycle Proteins; C000598308:FAM44B protein, mouse