Evidence map›Paper›PMID 36620995›Full record

ArticleDevelopment (Cambridge, England)2023

Single cell evaluation of endocardial Hand2 gene regulatory networks reveals HAND2-dependent pathways that impact cardiac morphogenesis.

Rajani M George, Beth A Firulli, Ram Podicheti, Douglas B Rusch, Brandon J Mannion, Len A Pennacchio, Marco Osterwalder, Anthony B Firulli

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Rajani M GeorgeHerman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA.ORCID 0000-0002-9153-5523
Beth A FirulliHerman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA.ORCID 0000-0001-6687-8949
Ram PodichetiCenter for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA.
Douglas B RuschCenter for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA.
Brandon J MannionEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.ORCID 0000-0002-1149-3790
Len A PennacchioEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Marco OsterwalderEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.ORCID 0000-0002-1969-2313
Anthony B FirulliHerman B Wells Center for Pediatric Research, Departments of Pediatrics, Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, IN 46202, USA.ORCID 0000-0001-6687-8949
Indiana University – Purdue University Indianapolis · USIndiana University Bloomington · USLawrence Berkeley National Laboratory · USUniversity of Bern · CH

Funding

Transcriptional regulation of cardiac morphogenesisP01HL134599 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI Anthony B. Firulli · 2017 to 2026
$25.7M
Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetR01HG003988 · NHGRI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Len Alexander Pennacchio · 2006 to 2026
$24.1M
Transcriptional regulation of cardiac conduction system morphogenesisR01HL145060 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B., SHOU, WEINIAN · 2019 to 2022
$2.8M
Gene Regulatory Networks that Establish Mandible and Maxilla PatterningR01DE029091 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI CLOUTHIER, DAVID E., FIRULLI, ANTHONY B. · 2020 to 2023
$2.4M
Endocardial mechanisms of cardiac trabeculation and septationR01HL120920 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.8M
NHGRI NIH HHS R01 HG003988NHLBI NIH HHS P01 HL134599NHLBI NIH HHS R01 HL120920NHLBI NIH HHS R01 HL145060NIDCR NIH HHS R01 DE029091NIH HHS 1R01DE02909
6 · The paper itself

Abstract

The transcription factor HAND2 plays essential roles during cardiogenesis. Hand2 endocardial deletion (H2CKO) results in tricuspid atresia or double inlet left ventricle with accompanying intraventricular septum defects, hypo-trabeculated ventricles and an increased density of coronary lumens. To understand the regulatory mechanisms of these phenotypes, single cell transcriptome analysis of mouse E11.5 H2CKO hearts was performed revealing a number of disrupted endocardial regulatory pathways. Using HAND2 DNA occupancy data, we identify several HAND2-dependent enhancers, including two endothelial enhancers for the shear-stress master regulator KLF2. A 1.8 kb enhancer located 50 kb upstream of the Klf2 TSS imparts specific endothelial/endocardial expression within the vasculature and endocardium. This enhancer is HAND2-dependent for ventricular endocardium expression but HAND2-independent for Klf2 vascular and valve expression. Deletion of this Klf2 enhancer results in reduced Klf2 expression within ventricular endocardium. These data reveal that HAND2 functions within endocardial gene regulatory networks including shear-stress response.

Indexed as

EndocardiumGene Regulatory NetworksAnimalsBasic Helix-Loop-Helix ProteinsGene Expression Regulation, DevelopmentalMiceMorphogenesisTranscription FactorsBasic Helix-Loop-Helix ProteinsHand2 protein, mouseTranscription FactorsCardiogenesisCongenital heart defectsEndocardial developmentHAND factorsMouse

Identifiers

PMID36620995
PMCPMC10110492
OpenAlexW4313826026

What Socratic 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 Socratic graph.