ER71 Acts Downstream of BMP, Notch, and Wnt Signaling in Blood and Vessel Progenitor Specification

Lee, Dongjun; Park, Changwon; Lee, Ho; Lugus, Jesse J.; Kim, Seok Hyung; Arentson, Elizabeth; Chung, Yun Shin; Gomez, Gustavo A.; Kyba, Michael; Lin, Shuo; Janknecht, Ralf; Lim, Dae–Sik; Choi, Kyunghee

doi:10.1016/j.stem.2008.03.008

Cited by 309 publications

(509 citation statements)

References 41 publications

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“…It is interesting that the expression of mouse Etv2 was transiently detected in the beginning of hematopoiesis and was barely detectable in hematopoietic tissues at later stages, such as the aortagonad-mesonephros and fetal liver in embryos and in the bone marrow and spleen in adults (54)(55)(56). A dramatic down-regulation of Etv2 during hematopoietic differentiation is also observed in zebrafish (35) and Xenopus (57).…”

Section: Discussionmentioning

confidence: 99%

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

Takeuchi

Fuse

Watanabe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The hemangioblast is a progenitor cell with the capacity to give rise to both hematopoietic and endothelial progenitors. Currently, the regulatory mechanisms underlying hemangioblast formation are being elucidated, whereas those controllers for the selection of hematopoietic or endothelial fates still remain a mystery. To answer these questions, we screened for zebrafish mutants that have defects in the hemangioblast expression of Gata1, which is never expressed in endothelial progenitors. One of the isolated mutants, it627, showed not only down-regulation of hematopoietic genes but also up-regulation of endothelial genes. We identified the gene responsible for the it627 mutant as the zebrafish homolog of Lys-specific demethylase 1 (LSD1/KDM1A). Surprisingly, the hematopoietic defects in lsd1it627 embryos were rescued by the gene knockdown of the Ets variant 2 gene (etv2), an essential regulator for vasculogenesis. Our results suggest that the LSD1-dependent shutdown of Etv2 gene expression may be a significant event required for hemangioblasts to initiate hematopoietic differentiation.

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Section: Discussionmentioning

confidence: 99%

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

Takeuchi

Fuse

Watanabe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Recent reports revealing Nkx2-5 expression in the endocardium (10) and the endocardial fate of the Nkx2-5-expressing cardiac progenitors (4-6) support the hypothesis that Nkx2-5 is an important regulator of the endothelial/ endocardial lineage during cardiogenesis although the molecular mechanisms are unknown. Recent studies in mice (24) and zebrafish (25,26) have reported that Etsrp71/ER71 is essential for the genesis of endothelial/endocardial lineage in the developing embryos. However, the transcriptional regulation of Etsrp71 was unclear.…”

Section: Discussionmentioning

confidence: 99%

Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo

Ferdous

Caprioli²,

Iacovino

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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298

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Recent studies support the existence of a common progenitor for the cardiac and endothelial cell lineages, but the underlying transcriptional networks responsible for specification of these cell fates remain unclear. Here we demonstrated that Ets-related protein 71 (Etsrp71), a newly discovered ETS family transcription factor, was a novel downstream target of the homeodomain protein, Nkx2-5. Using genetic mouse models and molecular biological techniques, we demonstrated that Nkx2-5 binds to an evolutionarily conserved Nkx2-5 response element in the Etsrp71 promoter and induces the Etsrp71 gene expression in vitro and in vivo. Etsrp71 was transiently expressed in the endocardium/endothelium of the developing embryo (E7.75-E9.5) and was extinguished during the latter stages of development. Using a gene disruption strategy, we found that Etsrp71 mutant embryos lacked endocardial/endothelial lineages and were nonviable. Moreover, using transgenic technologies and transcriptional and chromatin immunoprecipitation (ChIP) assays, we further established that Tie2 is a direct downstream target of Etsrp71. Collectively, our results uncover a novel functional role for Nkx2-5 and define a transcriptional network that specifies an endocardial/endothelial fate in the developing heart and embryo.cardiac progenitor cells ͉ endocardium ͉ Etsrp71 ͉ Tie2 ͉ cardiac development

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“…demonstrated that in the presence of VEGF, BMP-4 is able to induce hematopoietic differentiation of mouse ES cells in serumfree culture. Recently, Lee et al [37] showed that ER71, a member of the Ets transcription factor family, functions downstream of BMPs and regulates the generation of Flk1 + blood and vessel progenitors. These Flk1 + cells are able to differentiate into all types of myeloid and lymphoid progeny [38].…”

Section: Mesoderm Derivativesmentioning

confidence: 99%

Roles of TGF-β family signaling in stem cell renewal and differentiation

2008

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ER71 Acts Downstream of BMP, Notch, and Wnt Signaling in Blood and Vessel Progenitor Specification

Cited by 309 publications

References 41 publications

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2

Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo

Roles of TGF-β family signaling in stem cell renewal and differentiation

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