title: Brief report: VGLL4 is a novel regulator of survival in human embryonic stem cells.
abstract: Human embryonic stem cells (hESCs) are maintained in a self-renewing state by an interconnected network of mechanisms that sustain pluripotency, promote proliferation and survival, and prevent differentiation. We sought to find novel genes that could contribute to one or more of these processes using a gain-of-function screen of a large collection of human open reading frames. We identified Vestigial-like 4 (VGLL4), a cotranscriptional regulator with no previously described function in hESCs, as a positive regulator of survival in hESCs. Specifically, VGLL4 overexpression in hESCs significantly decreases cell death in response to dissociation stress. Additionally, VGLL4 overexpression enhances hESC colony formation from single cells. These effects may be attributable, in part, to a decreased activity of initiator and effector caspases observed in the context of VGLL4 overexpression. Additionally, we show an interaction between VGLL4 and the Rho/Rock pathway, previously implicated in hESC survival. This study introduces a novel gain-of-function approach for studying hESC maintenance and presents VGLL4 as a previously undescribed regulator of this process. Stem Cells 2013;31:2833-2841.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Tajonar
authors.forename: René
authors.initials: R
authors.lastname: Maehr
authors.forename: Guang
authors.initials: G
authors.lastname: Hu
authors.forename: Julie B
authors.initials: JB
authors.lastname: Sneddon
authors.forename: José
authors.initials: J
authors.lastname: Rivera-Feliciano
authors.forename: Dena E
authors.initials: DE
authors.lastname: Cohen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D014157:Transcription Factors; C488533:VGLL4 protein, human; D054460:rho-Associated Kinases
keywords: Apoptosis; Pluripotent stem cells; Rho-associated kinases; VGLL4 protein