Evidence map›Paper›PMID 40832854›Full record

ArticleCardiovascular research2025

The pioneer factor, ETV2, regulates networks to specify the embryonic endothelial lineage.

Satyabrata Das, Xiao Ma, Kidus Hailemariam, Javier E Sierra-Pagan, Thijs A Larson, Young Geun Choi, Anh Quynh Le, Riley J Leonard, Austin Cho, Hesham A Sadek and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Satyabrata DasCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0001-9790-6164
Xiao MaCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Kidus HailemariamCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Javier E Sierra-PaganCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Thijs A LarsonCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Young Geun ChoiCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Anh Quynh LeCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Riley J LeonardCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Austin ChoCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Hesham A SadekDivision of Cardiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Jianyi Jay ZhangDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, USA.ORCID 0000-0002-3955-6554
Mary G GarryCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Xiao DongMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN 55455, USA.
Wuming GongCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Daniel J GarryCardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.

Funding

Project 3 - Role of Proline Metabolism in Regulation of Mammalian Cardiomyocyte ProliferationP01HL160476 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Jianyi Zhang · 2022 to 2026
$13.1M
NHLBI NIH HHS P01 HL160476
6 · The paper itself

Abstract

aimsMechanisms that govern the emergence of multiple cell lineages from common mesodermal progenitors remain incompletely understood due to their limited number and accessibility. The pioneer transcription factor ETV2 sits at the top of the hematoendothelial (HE) lineage development molecular networks and directs both differentiation and reprogramming of endothelial lineage. In this study, we uncovered the transcriptional and epigenetic changes orchestrated by ETV2 to promote the HE lineage while suppressing other mesodermal lineages. METHODS AND

resultsWe isolated cells poised for skeletal muscle, cardiac and HE progenitor lineages by fluorescence activated cell sorting using the mouse embryonic stem cell-embryoid body (ES-EB) differentiation system over multiple time points with and without ETV2 overexpression. Analyzing these progenitor cells primed for distinct and different fate choices by single-cell RNA-sequencing and transposase-accessible chromatin sequencing (ATAC-seq), we defined the enhancers, transcriptional and epigenetic regulatory networks employed by ETV2 for its pioneer activity during HE lineage development. Overexpression of ETV2 directed the pluripotent cells towards a highly efficient generation of HE lineage at the expense of cardiac and skeletal muscle cell lineages. Dosage of ETV2 expression determined the sub-lineages of the HE progenitors. Tlr3 and Tlr4 were discovered as direct downstream targets of ETV2 contributing to the HE lineage development and their expression was dependent on ETV2 using overexpressing and null EBs. Master regulators of the cardiac lineage including Mesp1 were identified to be directly repressed by ETV2 in a context dependent fashion to suppress cardiac development in ETV2 overexpression cells. Repression of Mesp1 expression by ETV2 was further validated using Etv2 knock out (KO) EBs as well as stage-matched wild type (WT) and Etv2 null mouse embryos. Direct binding and down-regulation of Mesp1 by ETV2 overexpression was verified by chromatin immunoprecipitation sequencing, electrophoretic mobility shift assay (EMSA) and qPCR.

conclusionCollectively, our results define the functional role(s) played by ETV2 expression levels in the differential promotion and suppression of alternate fate choices of the mesodermal progenitor cells.

Indexed as

Cell LineageEndothelial Progenitor CellsGene Expression Regulation, DevelopmentalGene Regulatory NetworksTranscription FactorsAnimalsCell DifferentiationCells, CulturedCellular ReprogrammingChromatin Immunoprecipitation SequencingEmbryoid BodiesEpigenesis, GeneticFemaleGene Knockout TechniquesMesodermMiceER71 protein, mouseTLR3 protein, mouseTlr4 protein, mouseToll-Like Receptor 3Toll-Like Receptor 4Transcription FactorsEBsEndothelial lineageETV2MESP1Pioneer factorTLR3/TLR4

Identifiers

PMID40832854
PMCPMC13370475

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.