Differential Etv2 threshold requirement for endothelial and erythropoietic development.

Autor:	Sinha T; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Lammerts van Bueren K; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Dickel DE; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, 1 Cyclotron Road, Berkeley, CA 94720, USA; Comparative Biochemistry Program, University of California, Berkeley, Berkeley, CA 94720, USA., Zlatanova I; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Thomas R; Gladstone Institutes, San Francisco, San Francisco, CA 94158, USA., Lizama CO; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Xu SM; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Zovein AC; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA., Ikegami K; Division of Molecular and Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA., Moskowitz IP; Departments of Pediatrics, Pathology, and Human Genetics, University of Chicago, Chicago, IL 60637, USA., Pollard KS; Gladstone Institutes, San Francisco, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA 94158, USA., Pennacchio LA; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, 1 Cyclotron Road, Berkeley, CA 94720, USA; Comparative Biochemistry Program, University of California, Berkeley, Berkeley, CA 94720, USA., Black BL; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: brian.black@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 May 31; Vol. 39 (9), pp. 110881.
DOI:	10.1016/j.celrep.2022.110881
Abstrakt:	Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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