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Sustained Intrinsic WNT and BMP4 Activation Impairs HESC Differentiation to Definitive Endoderm and Drives the Cells Towards Extra-embryonic Mesoderm

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Journal Sci Rep
Specialty Science
Date 2021 Apr 16
PMID 33859268
Citations 3
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Abstract

We identified a human embryonic stem cell subline that fails to respond to the differentiation cues needed to obtain endoderm derivatives, differentiating instead into extra-embryonic mesoderm. RNA-sequencing analysis showed that the subline has hyperactivation of the WNT and BMP4 signalling. Modulation of these pathways with small molecules confirmed them as the cause of the differentiation impairment. While activation of WNT and BMP4 in control cells resulted in a loss of endoderm differentiation and induction of extra-embryonic mesoderm markers, inhibition of these pathways in the subline restored its ability to differentiate. Karyotyping and exome sequencing analysis did not identify any changes in the genome that could account for the pathway deregulation. These findings add to the increasing evidence that different responses of stem cell lines to differentiation protocols are based on genetic and epigenetic factors, inherent to the line or acquired during cell culture.

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References
1.
Gifford C, Ziller M, Gu H, Trapnell C, Donaghey J, Tsankov A . Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell. 2013; 153(5):1149-63. PMC: 3709577. DOI: 10.1016/j.cell.2013.04.037. View

2.
Maitra A, Arking D, Shivapurkar N, Ikeda M, Stastny V, Kassauei K . Genomic alterations in cultured human embryonic stem cells. Nat Genet. 2005; 37(10):1099-103. DOI: 10.1038/ng1631. View

3.
Nguyen H, Geens M, Mertzanidou A, Jacobs K, Heirman C, Breckpot K . Gain of 20q11.21 in human embryonic stem cells improves cell survival by increased expression of Bcl-xL. Mol Hum Reprod. 2013; 20(2):168-77. DOI: 10.1093/molehr/gat077. View

4.
Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

5.
Butcher L, Ito M, Brimpari M, Morris T, Soares F, Ahrlund-Richter L . Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells. Nat Commun. 2016; 7:10458. PMC: 4740175. DOI: 10.1038/ncomms10458. View