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Alternative pre-mRNA splicing switch controls hESC pluripotency and differentiation.
Genes Dev. 2018 09 01; 32(17-18):1103-1104.GD

Abstract

Alternative splicing (AS) of pre-mRNAs is a ubiquitous process in mammals that is tightly regulated in a cell type- and cell state-dependent manner. However, the details of how splicing is regulated to impact specific cell fate decisions remains incompletely understood. A study by Yamazaki and colleagues (pp. 1161-1174) in this issue of Genes & Development provides exciting new insight into the role and regulation of splicing in the maintenance of pluripotency of human embryonic stem cells (hESCs). In brief, they show that AS of several genes is robustly regulated upon differentiation of hESCs. One of these genes, T-cell factor 3 (TCF3), is regulated at least in part through the activity of heterogeneous nuclear ribonucleoproteins H1 and F (hnRNP H/F) to control the mutually exclusive expression of the encoded E12 and E47 transcription regulators. The investigators demonstrate that reduced expression of hnRNP H/F favors expression of E47, which in turn decreases E-cadherin expression to promote hESC differentiation. In contrast, high levels of hnRNP H/F induce expression of E12 to maintain pluripotency. Thus, this work provides at least one new link between AS and control of human stem cell fate and suggests a broader role of splicing in pluripotency.

Authors+Show Affiliations

Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review
Comment

Language

eng

PubMed ID

30181358

Citation

Agosto, Laura M., and Kristen W. Lynch. "Alternative pre-mRNA Splicing Switch Controls hESC Pluripotency and Differentiation." Genes & Development, vol. 32, no. 17-18, 2018, pp. 1103-1104.
Agosto LM, Lynch KW. Alternative pre-mRNA splicing switch controls hESC pluripotency and differentiation. Genes Dev. 2018;32(17-18):1103-1104.
Agosto, L. M., & Lynch, K. W. (2018). Alternative pre-mRNA splicing switch controls hESC pluripotency and differentiation. Genes & Development, 32(17-18), 1103-1104. https://doi.org/10.1101/gad.318451.118
Agosto LM, Lynch KW. Alternative pre-mRNA Splicing Switch Controls hESC Pluripotency and Differentiation. Genes Dev. 2018 09 1;32(17-18):1103-1104. PubMed PMID: 30181358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alternative pre-mRNA splicing switch controls hESC pluripotency and differentiation. AU - Agosto,Laura M, AU - Lynch,Kristen W, PY - 2018/9/6/entrez PY - 2018/9/6/pubmed PY - 2019/8/28/medline KW - E2A KW - T-cell factor 3 KW - alternative splicing KW - heterogeneous nuclear ribonucleoprotein KW - human embryonic stem cell SP - 1103 EP - 1104 JF - Genes & development JO - Genes Dev. VL - 32 IS - 17-18 N2 - Alternative splicing (AS) of pre-mRNAs is a ubiquitous process in mammals that is tightly regulated in a cell type- and cell state-dependent manner. However, the details of how splicing is regulated to impact specific cell fate decisions remains incompletely understood. A study by Yamazaki and colleagues (pp. 1161-1174) in this issue of Genes & Development provides exciting new insight into the role and regulation of splicing in the maintenance of pluripotency of human embryonic stem cells (hESCs). In brief, they show that AS of several genes is robustly regulated upon differentiation of hESCs. One of these genes, T-cell factor 3 (TCF3), is regulated at least in part through the activity of heterogeneous nuclear ribonucleoproteins H1 and F (hnRNP H/F) to control the mutually exclusive expression of the encoded E12 and E47 transcription regulators. The investigators demonstrate that reduced expression of hnRNP H/F favors expression of E47, which in turn decreases E-cadherin expression to promote hESC differentiation. In contrast, high levels of hnRNP H/F induce expression of E12 to maintain pluripotency. Thus, this work provides at least one new link between AS and control of human stem cell fate and suggests a broader role of splicing in pluripotency. SN - 1549-5477 UR - https://www.unboundmedicine.com/medline/citation/30181358/Alternative_pre_mRNA_splicing_switch_controls_hESC_pluripotency_and_differentiation_ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=30181358 DB - PRIME DP - Unbound Medicine ER -