Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast
The role of genomic variation in differentiation is currently not well understood. Here, the genomic variations were determined with the whole-genome sequencing for three pairs of pluripotent stem cell lines and their corresponding BMP4-induced trophoblast cell lines. We identified ∼3,500 single nuc...
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doaj-73ab951fb1d84667aec4390f39b76c682020-11-25T03:15:24ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-04-011110.3389/fgene.2020.00230518254Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to TrophoblastHai-tao Li0Yajun Liu1Yajun Liu2Yajun Liu3Hongde Liu4Xiao Sun5State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaThe Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences of Zhengzhou University Translational Medicine Platform, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaThe role of genomic variation in differentiation is currently not well understood. Here, the genomic variations were determined with the whole-genome sequencing for three pairs of pluripotent stem cell lines and their corresponding BMP4-induced trophoblast cell lines. We identified ∼3,500 single nucleotide variations and ∼4,500 indels by comparing the genome sequenced data between the stem cell lines and the matched BMP4-induced trophoblast cell lines and annotated them by integrating the epigenomic and transcriptomic datasets. Relatively, introns enrich more variations. We found ∼45% (42 genes) of the differentially expressed genes in trophoblasts that associate genomic variations. Six variations, located at transcription factor binding sites where H3K4me3 and H3K27ac are enriched in both H1 and H1_BMP4, were identified. The epigenetic status around the genomic variations in H1 was similar to that in H1_BMP4. This means that the variation-associated gene’s expression change can not be attributed to epigenetic alteration. The genes associated with the six variations were upregulated in differentiation. We inferred that during the differentiation, an increased in the expression level of the MEF2C gene is due to a genomic variation in chromosomes 5: 88179358 A > G, which is at a binding site of TFs KLF16, NR2C2, and ZNF740 to MEF2C. Allele G shows a higher affinity to the TFs in the induced cells. The increased expression of MEF2C leads to an increased expression of TF MEF2C’s target genes, subsequently affecting the differentiation. Although genomic variation should not be a dominant factor in differentiation, we believe that genomic variation could indeed play a role in the differentiation from stem cells into trophoblast.https://www.frontiersin.org/article/10.3389/fgene.2020.00230/fullgenomic variationspluripotent stem cellstrophoblastwhole genome sequencingepigenomic and transcriptomic data |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hai-tao Li Yajun Liu Yajun Liu Yajun Liu Hongde Liu Xiao Sun |
spellingShingle |
Hai-tao Li Yajun Liu Yajun Liu Yajun Liu Hongde Liu Xiao Sun Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast Frontiers in Genetics genomic variations pluripotent stem cells trophoblast whole genome sequencing epigenomic and transcriptomic data |
author_facet |
Hai-tao Li Yajun Liu Yajun Liu Yajun Liu Hongde Liu Xiao Sun |
author_sort |
Hai-tao Li |
title |
Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast |
title_short |
Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast |
title_full |
Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast |
title_fullStr |
Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast |
title_full_unstemmed |
Effect for Human Genomic Variation During the BMP4-Induced Conversion From Pluripotent Stem Cells to Trophoblast |
title_sort |
effect for human genomic variation during the bmp4-induced conversion from pluripotent stem cells to trophoblast |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2020-04-01 |
description |
The role of genomic variation in differentiation is currently not well understood. Here, the genomic variations were determined with the whole-genome sequencing for three pairs of pluripotent stem cell lines and their corresponding BMP4-induced trophoblast cell lines. We identified ∼3,500 single nucleotide variations and ∼4,500 indels by comparing the genome sequenced data between the stem cell lines and the matched BMP4-induced trophoblast cell lines and annotated them by integrating the epigenomic and transcriptomic datasets. Relatively, introns enrich more variations. We found ∼45% (42 genes) of the differentially expressed genes in trophoblasts that associate genomic variations. Six variations, located at transcription factor binding sites where H3K4me3 and H3K27ac are enriched in both H1 and H1_BMP4, were identified. The epigenetic status around the genomic variations in H1 was similar to that in H1_BMP4. This means that the variation-associated gene’s expression change can not be attributed to epigenetic alteration. The genes associated with the six variations were upregulated in differentiation. We inferred that during the differentiation, an increased in the expression level of the MEF2C gene is due to a genomic variation in chromosomes 5: 88179358 A > G, which is at a binding site of TFs KLF16, NR2C2, and ZNF740 to MEF2C. Allele G shows a higher affinity to the TFs in the induced cells. The increased expression of MEF2C leads to an increased expression of TF MEF2C’s target genes, subsequently affecting the differentiation. Although genomic variation should not be a dominant factor in differentiation, we believe that genomic variation could indeed play a role in the differentiation from stem cells into trophoblast. |
topic |
genomic variations pluripotent stem cells trophoblast whole genome sequencing epigenomic and transcriptomic data |
url |
https://www.frontiersin.org/article/10.3389/fgene.2020.00230/full |
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