Blf and drl cluster synergistically regulate cell fate commitment during zebrafish primitive hematopoiesis.
Xue ZhangYuxi YangYuxuan WeiQingshun ZhaoXin LouPublished in: Development (Cambridge, England) (2022)
Hematopoiesis is a highly coordinated process that generates all the body's blood cells, perturbations in embryonic hematopoiesis may result in illnesses ranging from fetal anemia to various leukemias. Correct establishment of hematopoietic progenitor cell fate is essential for development of adequate blood cell subpopulations, although controllers for cell fate commitment have not been fully defined. Here, we show that primary erythropoiesis and myelopoiesis in zebrafish embryos are synergistically regulated by blf and drl cluster; as simultaneous led to severe erythrocyte aplasia and excessive macrophage formation at the expense of neutrophil development. Integrative analysis of transcriptome and genome-wide binding data revealed blf and drl cluster genes are responsible for constraining expression of vasculogenesis-promoting genes in the intermediate cell mass and monocytopoiesis-promoting genes in the rostral blood island. This indicates that blf and drl cluster genes act as novel determinants of the fate commitment of erythroid and myeloid progenitor cells. Furthermore, we performed a rescue screen found that Zfp932 is a potential mammalian functional equivalent to zebrafish blf and drl cluster genes. Our data provide insight into conserved cell fate commitment mechanisms of primitive hematopoiesis.
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