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Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Danio rerio

PROVIDER: GSE158101 | GEO | 2022/01/14

REPOSITORIES: GEO

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Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development.

Project description:RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1-null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, although zebrafish embryos with a runx1 W84X mutation have defects in early definitive hematopoiesis, some runx1W84X/W84X embryos can develop to fertile adults with blood cells of multilineages, raising the possibility that HSCs can emerge without RUNX1. Here, using 3 new zebrafish runx1-/- lines, we uncovered the compensatory mechanism for runx1-independent hematopoiesis. We show that, in the absence of a functional runx1, a cd41-green fluorescent protein (GFP)+ population of hematopoietic precursors still emerge from the hemogenic endothelium and can colonize the hematopoietic tissues of the mutant embryos. Single-cell RNA sequencing of the cd41-GFP+ cells identified a set of runx1-/--specific signature genes during hematopoiesis. Significantly, gata2b, which normally acts upstream of runx1 for the generation of HSCs, was increased in the cd41-GFP+ cells in runx1-/- embryos. Interestingly, genetic inactivation of both gata2b and its paralog gata2a did not affect hematopoiesis. However, knocking out runx1 and any 3 of the 4 alleles of gata2a and gata2b abolished definitive hematopoiesis. Gata2 expression was also upregulated in hematopoietic cells in Runx1-/- mice, suggesting the compensatory mechanism is conserved. Our findings indicate that RUNX1 and GATA2 serve redundant roles for HSC production, acting as each other's safeguard.

| S-EPMC9153008 | biostudies-literature

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development

Project description:Here we used RNA sequencing to characterize the transcriptional profile of the total RNA from c-Kit+ cells of Runx1 KO and control mice.

2022-01-14 | GSE158100 | GEO

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development

Project description:We used single cell-RNA sequencing to investigate the expression and the heterogeneity of wild type and runx1-mutant cd41-GFPLow cd41GFP hematopoietic stem and progenitor cells at embryonic (2.5 days post fertilization, dpf) and larval stages (6, 10 16 dpf).

2022-01-14 | GSE158099 | GEO

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development

Project description:Here we used RNA sequencing to characterize the transcriptional profile of the kidney of runx1 knock out zebrafish adult compared to wild type.

2022-01-14 | GSE158098 | GEO

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development [zebrafish bulk RNA-seq2]

Project description:Here we used RNAsequencing to characterize the transcriptional profile of the kidney of runx1 knock out zebrafish adult compared to wild type.

2022-01-14 | GSE169689 | GEO