GSE51025 Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

Contributors : Andreia M Gomes ; Betty Chang ; Carlos-Filipe Pereira ; Kateri Moore ; Ihor R LemischkaSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensDuring development, hematopoietic stem/progenitor cells (HSPCs) arise fromspecialized endothelial cells by a process termed endothelial-to-hematopoietictransition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that human fibroblasts can be reprogrammed into hemogenic cells by the same transcription factors. Induced cells display dynamic EHT transcriptional programs, generate hematopoietic progeny, possess HSPC cell surface phenotype and repopulate immunodeficient mice for three months. Mechanistically, GATA2 and GFI1B interact and co-occupy a cohort of targets. This cooperative binding is reflected by engagement of open enhancers and promoters, initiating silencing of fibroblast genes and activating the hemogenic program. However, GATA2 displays dominant and independent targeting activity during the early phases of reprogramming. These findings shed light on the processes controlling human HSC specification ...

Source: GEO: Gene Expression Omnibus - December 4, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research