Dataset Information

ETV2 induces endothelial, but not hematopoietic, lineage specification in birds.

ABSTRACT: Cardiovascular system develops from the lateral plate mesoderm. Its three primary cell lineages (hematopoietic, endothelial, and muscular) are specified by the sequential actions of conserved transcriptional factors. ETV2, a master regulator of mammalian hemangioblast development, however, is absent in the chicken genome and acts downstream of NPAS4L in zebrafish. Here, we investigated the epistatic relationship between NPAS4L and ETV2 in avian hemangioblast development. We showed that ETV2 is deleted in all 363 avian genomes analyzed. Mouse ETV2 induced LMO2, but not NPAS4L or SCL, expression in chicken mesoderm. Squamate (lizards, geckos, and snakes) genomes contain both NPAS4L and ETV2 In Madagascar ground gecko, both genes were expressed in developing hemangioblasts. Gecko ETV2 induced only LMO2 in chicken mesoderm. We propose that both NPAS4L and ETV2 were present in ancestral amniote, with ETV2 acting downstream of NPAS4L in endothelial lineage specification. ETV2 may have acted as a pioneer factor by promoting chromatin accessibility of endothelial-specific genes and, in parallel with NPAS4L loss in ancestral mammals, has gained similar function in regulating blood-specific genes.

SUBMITTER: Weng W

PROVIDER: S-EPMC10992995 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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ETV2 induces endothelial, but not hematopoietic, lineage specification in birds.

Weng Wei W Deng Yuan Y Deviatiiarov Ruslan R Hamidi Sofiane S Kajikawa Eriko E Gusev Oleg O Kiyonari Hiroshi H Zhang Guojie G Sheng Guojun G

Life science alliance 20240403 6

Cardiovascular system develops from the lateral plate mesoderm. Its three primary cell lineages (hematopoietic, endothelial, and muscular) are specified by the sequential actions of conserved transcriptional factors. <i>ETV2</i>, a master regulator of mammalian hemangioblast development, however, is absent in the chicken genome and acts downstream of <i>NPAS4L</i> in zebrafish. Here, we investigated the epistatic relationship between NPAS4L and ETV2 in avian hemangioblast development. We showed ...[more]

PMID: 38570190

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Project description:BackgroundHematopoietic stem cells are able to self-renew and differentiate into all blood cell lineages. Hematopoietic stem cell transplantation is a mainstay of life-saving therapy for hematopoietic malignancies and hypoproliferative disorders. In vitro hematopoietic differentiation of human pluripotent stem cells (hPSCs) is a promising approach for modeling hematopoietic development and cell replacement therapies. Although using hPSCs to derive hematopoietic progenitor cells has achieved some successes in the past, differentiation from hPSCs to produce all hematopoietic cells which can provide robust long-term multilineage engraftment is still very difficult. Here, we reported a novel culture system for hematopoietic differentiation from human embryonic stem cells (hESCs) with optimal cytokines combinations under hypoxia condition.MethodsIn vitro production of T lineage hematopoietic stem/progenitor cells from hESCs by using hypoxia differentiation system, the effects and the potential mechanism of hypoxia promoting T lineage hematopoiesis were investigated by RT-qPCR validation, cell cycle assay and flow cytometry analysis.ResultsUsing our differentiation system, almost 80% CD45+ cells generated from hESCs were hematopoietic cells and particularly could be further induced into CD3+TCRαβ+ T cells in vitro. We detected more CD34+CD144+ hematopoietic endothelial progenitors (HEPs) induced from hESCs than those in normoxia conditions, and the early HEPs-related gene DLL4 was upregulated by enhancing the hypoxia signaling via potential HIF-1α/NOTCH1/DLL4 axis to enhance arterial feature, thus drove T lineage during the hematopoiesis. Strikingly, hematopoietic cells generated in our system exhibited the potential for all multilineage reconstruction including lymphoid, myeloid and erythroid lineages in vivo by transplantation assay.ConclusionOur results demonstrated that hypoxia plays an important role in T lineage hematopoiesis by promoting the expression of arterial endothelial gene DLL4 and upregulation of NOTCH1 through the activation of the HIF-1α signaling pathway. These results provide a significant approach for in vitro and in vivo production of fully functional hematopoietic stem/progenitor cells from hESCs.

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ETV2 induces endothelial, but not hematopoietic, lineage specification in birds.

Publications

ETV2 induces endothelial, but not hematopoietic, lineage specification in birds.

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