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The Caudal Hematopoietic Tissue is Differentially Required for Erythrocytes and Neutrophils from Definitive Hematopoiesis in Zebrafish

ABSTRACT: Neutrophils and erythrocytes are vital to the immune system and oxygen transport, respectively. However, the mechanisms by which hematopoietic niches support their development remain incompletely understood. In hematopoiesis research, zebrafish larvae are a common model for studying the development of definitive neutrophils and erythrocytes in the caudal hematopoietic tissue. In this study, we showed that erythrocytes predominantly reside inside the blood vessels of the CHT, while neutrophils stay outside. Ectopic vascular endothelium, induced by Bone Morphogenetic Protein 2b(Bmp2b) overexpression, attracts both cell types, with erythrocytes inside and neutrophils outside. CHT removal has minimal impact on definitive neutrophils from the ventral wall of the dorsal aorta (VDA) but severely affects definitive erythrocytes from the same source. Bulk RNA-sequencing identified epoa as a vital factor for erythrocyte generation within CHT endothelium. Overexpression of epoa through the lyve1b promoter, which is specifically expressed in vein, lymphatic vessels and CHT vein endothelial cells, rescued the erythrocyte reduction in epoa mutants. Our study reveals that the caudal hematopoietic tissue is differentially required for definitive erythrocytes and neutrophils.

ORGANISM(S): Danio rerio

PROVIDER: GSE247730 | GEO | 2023/11/16

REPOSITORIES: GEO

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Project description:Hematopoiesis is a well-established model system to study molecular mechanisms of lineage-specific differentiation. Key transcription factors (TFs), such as PU.1, NF-E2 and GATA1 are implicated in crucial aspects of distinct hematopoietic lineages. How TFs collaborate with histone modificatons and how they affect the chromatin status remains to be elucidated. Chromatin-Immunoprecipitation followed by next-generation sequencing (ChIP-seq) has been proven to be an excellent tool to study chromatin modifications genome-wide. In this study, ChIP-seq was used to investigate the H3K4me2 landscape at enhancers during hematopoietic differentiation, starting from the hematopoietic stem cell (HSC) up to the fully differentiated erythrocyte, megakaryocyte or granulocyte. Although cell morphology and gene expression profiles differ extensively in committed erythrocytes, megakaryocytes and granulocytes, the genomic landscape of H3K4me2 is surprisingly alike across the three cell types. Granulocytes, in particular, seem to display an ‘erythocyte-like’ chromatin pattern. Similar results were observed for another chromatin mark, H3K27ac. Unexpectedly, the common progenitors of erythrocytes and granulocytes do not display a similar chromatin pattern, excluding the idea that the H3K4me2 mark is placed early on during differentiation. These results also suggest that the chromatin state is probably not the determining factor for lineage differentiation, but that rather lineage specific TF binding is important. In agreement with this, mature megakaryocytes loose the H3K4me2 mark surrounding erythrocyte-specific genes. This might be explained because megakaryocytes and erythrocytes both express the lineage specific TFs GATA1 and NF-E2. Altogether, we show that committed granulocytes and erythrocytes display similar H3K4me2 and H3K27ac patterns, and that those marks alone cannot predict which genes will be expressed eventually. Genomic ChIP-Seq on key transcription factors and histone modification marks in hematopoiesis

Dataset Information

The Caudal Hematopoietic Tissue is Differentially Required for Erythrocytes and Neutrophils from Definitive Hematopoiesis in Zebrafish

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