Brief Report: VGLL4 Is a Novel Regulator of Survival in Human Embryonic Stem Cells

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 usin...

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Published inStem cells (Dayton, Ohio) Vol. 31; no. 12; pp. 2833 - 2841
Main Authors Tajonar, Adriana, Maehr, René, Hu, Guang, Sneddon, Julie B., Rivera‐Feliciano, José, Cohen, Dena E., Elledge, Stephen J., Melton, Douglas A.
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.12.2013
Subjects
Animals
Apoptosis
Apoptosis - physiology
Caspase
Cell Differentiation - physiology
Cell Survival - physiology
Cells, Cultured
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Humans
Medical research
Mice
Mice, SCID
Pluripotent stem cells
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
rho-Associated Kinases - metabolism
Rho‐associated kinases
Stem cells
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription Factors - physiology
VGLL4 protein
VGLL4 protein
Rho-associated kinases
Pluripotent stem cells
Apoptosis
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Summary: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
Bibliography:Author contributions: A.T.: conception and design, provision of study material, collection and assembly of data, data analysis and interpretation, and manuscript writing; R.M. and G.H.: conception and design, provision of study material, and data analysis and interpretation; J.B.S.: data analysis and interpretation; J.R.: conception and design and data analysis and interpretation; D.E.C.: conception and design, administrative support, and manuscript writing; S.J.E.: conception and design, financial support, administrative support, and final approval of manuscript; D.A.M.: conception and design, financial support, administrative support, manuscript writing, and final approval of manuscript.
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ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1445