The Flk1-Cre-mediated deletion of ETV2 defines its narrow temporal requirement during embryonic hematopoietic development.

Stem Cells
Sarah WareingValerie Kouskoff

Abstract

During embryonic development, the emergence of hematopoiesis and vasculogenesis is tightly associated, with many transcription factors implicated in both developmental processes. Among those factors, ETV2 acts at the top of the hierarchy and controls the formation of both lineages. However, it is not known at which stage of mesoderm development ETV2 is acting and whether ETV2 activity is further required once mesodermal precursors have been specified to the hematopoietic and endothelial fates. In this study, we characterize the developmental window during which ETV2 expression is required for hematopoietic and endothelial development. Using cre-mediated deletion of ETV2, we demonstrate that ETV2 is acting prior to or at the time of FLK1 expression in mesodermal precursors to initiate the hematopoietic and endothelial program. Using the in vitro differentiation of embryonic stem cells as a model system, we further show that ETV2 re-expression in Etv2(-/-) Flk1-negative precursors drives hematopoiesis specification and switches on the expression of most genes known to be implicated in hematopoietic and endothelial development. Among the downstream targets of ETV2, we identify the transcription factors SCL, GATA2, and FLI1 known t...Continue Reading

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Citations

Nov 28, 2012·PloS One·Tara L RasmussenDaniel J Garry
Aug 10, 2013·Blood Cells, Molecules & Diseases·Aldo Ciau-UitzFeng Liu
Aug 21, 2013·Blood Cells, Molecules & Diseases·Victoria MoignardBerthold Göttgens
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Jun 27, 2012·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Sarah WareingValerie Kouskoff
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Mar 23, 2011·Stem Cell Research·Adam OskowitzRadhika Pochampally
Dec 28, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Haiyong ZhaoKyunghee Choi
Feb 10, 2017·Blood·Catherine PorcherMaiken S Kristiansen
Apr 27, 2018·Current Opinion in Hematology·Kyunghee Choi
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Nov 20, 2019·Development·Haiyong Zhao, Kyunghee Choi
Sep 2, 2017·Cardiovascular Research·Naoko Koyano-Nakagawa, Daniel J Garry

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