ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/010/SRR15193610/SRR15193610.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/011/SRR15193611/SRR15193611.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/015/SRR15193615/SRR15193615.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/014/SRR15193614/SRR15193614.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/012/SRR15193612/SRR15193612.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/013/SRR15193613/SRR15193613.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR151/009/SRR15193609/SRR15193609.fastq.gzprimaryOK200GenomicsStem Cell Biology and Cellular Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA748065Homo sapiensDNA methyltransferase 3A (DNMT3A) is the most frequently mutated gene in clonal hematopoiesis, indicating that it may be essential for hematopoietic differentiation. We therefore addressed the functional relevance of DNMT3A for hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) by knocking out either exon 2, 19, or 23. Directed differentiation towards mesenchymal stromal cells or hematopoietic progenitor cells (iHPCs) was only slightly reduced in exon 19-/- lines. Notably, exon 19-/- and exon 23-/- lines revealed absence of almost the entire de novo DNA methylation during differentiation. Despite the drastic effects on DNA methylation, there was no significant impact on gene expression of iHPCs. Notably, DNA methylation differences in acute myeloid leukemia with/without DNMT3A are related to iHPCs with/without DNMT3A knockout. Our results demonstrate that de novo DNA methylation during hematopoietic differentiation of iPSCs is almost entirely dependent on DNMT3A, while it has little impact on early cell-fate decisions. Overall design: RNA from iPSC-derived hematopoietic progenitor cells was isolated after 16 days of hematopoietic differentiation and sequenced on a HiSeq2500v4 sequencer.xref:PubMed:35705990ENADNA MTase MmuIIIA, DNA MTase HsaIIIA, DNA methyltransferase HsaIIIA, de novo DNA methylation, DNA methylation involved in embryo development, human being, Man (Taxonomy), TBRS, DNA methyltransferase MmuIIIA, 2.1.1.37, Mini-Exons, Modern, M.MmuIIIA, Exon, Mini Exon, Dnmt3a, DNMT3A2, RNA-seq., human, Human, loss of, iPSC, Homo sapiens, post-fertilization epigenetic regulation of gene expression, Modern Man, Mini-Exon, M.HsaIIIA, Whole Transcriptome Shotgun Sequencing, iPS cell, Man, MmuIIIA, epigenetic regulation of embryonic gene expressionDNA MTase MmuIIIA, DNA MTase HsaIIIA, DNA methyltransferase HsaIIIA, de novo DNA methylation, DNA methylation involved in embryo development, human being, Man (Taxonomy), TBRS, DNA methyltransferase MmuIIIA, 2.1.1.37, Mini-Exons, Modern, M.MmuIIIA, Exon, Mini Exon, Dnmt3a, DNMT3A2, RNA-seq., human, Human, loss of, iPSC, Homo sapiens, post-fertilization epigenetic regulation of gene expression, Modern Man, Mini-Exon, M.HsaIIIA, Whole Transcriptome Shotgun Sequencing, iPS cell, Man, MmuIIIA, epigenetic regulation of embryonic gene expressionfalseHematopoietic differentiation of human iPSC is hardly affected by knockouts in DNMT3A exons despite loss of de novo DNA methylation [RNA-seq]Hematopoietic differentiation of human iPSC is hardly affected by knockouts in DNMT3A exons despite loss of de novo DNA methylation [RNA-seq]2025-09-242022-06-03PRJNA748065GSE180403960635705990