TCF3 alternative splicing controlled by hnRNP H/F regulates E-cadherin expression and hESC pluripotency [Research Papers]

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.

Source: Genes and Development - September 4, 2018 Category: Genetics & Stem Cells Authors: Yamazaki, T., Liu, L., Lazarev, D., Al-Zain, A., Fomin, V., Yeung, P. L., Chambers, S. M., Lu, C.-W., Studer, L., Manley, J. L. Tags: Research Papers Source Type: research