AI Article Synopsis
- This study focuses on alternative splicing (AS) and its significance in the differentiation of embryonic stem cells (ESCs), particularly in human ESCs (hESCs).
- Researchers found that specific alternative splicing patterns in hESCs lead to the production of two isoforms of the T-cell factor 3 (TCF3) transcription factor, E12 and E47, which are regulated by the splicing factors hnRNP H and F.
- The levels of hnRNP H/F are high in hESCs, promoting E12 expression, but decrease during differentiation, causing a switch to E47; this shift is critical because E47 represses important genes like E-cadherin that help maintain plur
Article Abstract
Alternative splicing (AS) plays important roles in embryonic stem cell (ESC) differentiation. In this study, we first identified transcripts that display specific AS patterns in pluripotent human ESCs (hESCs) relative to differentiated cells. One of these encodes T-cell factor 3 (TCF3), a transcription factor that plays important roles in ESC differentiation. AS creates two TCF3 isoforms, E12 and E47, and we identified two related splicing factors, heterogeneous nuclear ribonucleoproteins (hnRNPs) H1 and F (hnRNP H/F), that regulate TCF3 splicing. We found that hnRNP H/F levels are high in hESCs, leading to high E12 expression, but decrease during differentiation, switching splicing to produce elevated E47 levels. Importantly, hnRNP H/F knockdown not only recapitulated the switch in TCF3 AS but also destabilized hESC colonies and induced differentiation. Providing an explanation for this, we show that expression of known TCF3 target E-cadherin, critical for maintaining ESC pluripotency, is repressed by E47 but not by E12.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120717 | PMC |
| http://dx.doi.org/10.1101/gad.316984.118 | DOI Listing |
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