Evidence mapPaperPMID 40495012Full record

ArticleNature cardiovascular research2025

Pioneer factor ETV2 safeguards endothelial cell specification by recruiting the repressor REST to restrict alternative lineage commitment.

Danyang Chen, Xiaonuo Fan, Ninghe Sun, Kai Wang, Liyan Gong, Juan M Melero-Martin, William T Pu

Abstract read
In one paragraph

Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Danyang ChenDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Xiaonuo FanDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Ninghe SunProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Kai WangDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.
Liyan GongDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.
Juan M Melero-MartinDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4689-8149
William T PuDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA. william.pu@cardio.chboston.org.ORCID http://orcid.org/0000-0002-4551-8079

Funding

Regulation of endothelial cell specificationR01HL151450 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Juan M Melero-Martin, William Tswenching Pu · 2022 to 2022
$652k
American Heart Association (American Heart Association, Inc.) 23POST1019621NHLBI NIH HHS R01 HL151450U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL151450
6 · The paper itself

Abstract

Mechanisms of cell fate specification are central to developmental biology and regenerative medicine. ETV2 is a master regulator for the endothelial cell (EC) lineage specification. Here we study mechanisms by which ETV2 overexpression in human induced pluripotent stem-cell-derived mesodermal progenitors efficiently specifies ECs. We used CUT&RUN, scRNA-seq and scATAC-seq to characterize the molecular features of EC differentiation mediated by ETV2. We defined the scope of ETV2 pioneering activity and identified its direct downstream target genes. Induced ETV2 expression both directed specification of endothelial progenitors and suppressed acquisition of alternative fates. Functional screening and candidate validation revealed cofactors essential for efficient EC specification, including the transcriptional activator GABPA. Notably, the transcriptional repressor REST was also necessary for efficient EC specification. ETV2 recruited REST to repress non-EC lineage genes. Our study provides an unparalleled molecular analysis of EC specification at single-cell resolution and highlights the important role of pioneer factors to recruit repressors that suppress commitment to alternative lineages.

Indexed as

Cell DifferentiationCell LineageEndothelial CellsEndothelial Progenitor CellsInduced Pluripotent Stem CellsRepressor ProteinsTranscription FactorsGene Expression Regulation, DevelopmentalHumansRE1-Silencing Transcription FactorSingle-Cell AnalysisETV2 protein, humanRE1-Silencing Transcription FactorRepressor ProteinsTranscription Factors

Identifiers

PMID40495012
PMCPMC12836307

What Socratic holds

Textmetadata
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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 Socratic graph.