Evidence map›Paper›PMID 34492681›Full record

ArticleBlood advances2021

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development.

Erica Bresciani, Blake Carrington, Kai Yu, Erika M Kim, Tao Zhen, Victoria Sanchez Guzman, Elizabeth Broadbridge, Kevin Bishop, Martha Kirby, Ursula Harper and 5 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

15 citing papers in PubMed, 18 citations in OpenAlex.

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  13. Zebrafish: a convenient tool for myelopoiesis research.Cell regeneration (London, England) · 2023
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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

15 authors at 4 institutions in 2 countries.

Erica BrescianiOncogenesis and Development Section.
Blake CarringtonZebrafish Core.
Kai YuOncogenesis and Development Section.ORCID 0000-0002-2561-8160
Erika M KimOncogenesis and Development Section.
Tao ZhenOncogenesis and Development Section.
Victoria Sanchez GuzmanOncogenesis and Development Section.
Elizabeth BroadbridgeOncogenesis and Development Section.
Kevin BishopZebrafish Core.
Martha KirbyFlow Cytometry Core.ORCID 0000-0001-7157-7964
Ursula HarperGenomics Core.
Stephen WincovitchCytogenetics and Microscopy Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Stefania Dell'OrsoNext Generation Sequencing Unit, Office of Science and Technology.
Vittorio SartorelliLaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD.
Raman SoodOncogenesis and Development Section.ORCID 0000-0001-5565-662X
Paul LiuOncogenesis and Development Section.ORCID 0000-0002-6779-025X
Zebra Technologies (United States) · USNational Institutes of Health · USGenomics (United Kingdom) · GBOffice of Science · US

Funding

Control of Myogenesis and Regulation of MyoD Post-Transcriptional ModificationsZIAAR041126 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SARTORELLI, VITTORIO · 2009 to 2025
$28.7M
High Throughput Next Generation Sequencing: supports genomics and epigenomics research in muscle, skin, bone and autoimmune diseases.ZICAR041207 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI DELL'ORSO, STEFANIA · 2016 to 2025
$12.3M
6 · The paper itself

Abstract

RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1-null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, although zebrafish embryos with a runx1 W84X mutation have defects in early definitive hematopoiesis, some runx1W84X/W84X embryos can develop to fertile adults with blood cells of multilineages, raising the possibility that HSCs can emerge without RUNX1. Here, using 3 new zebrafish runx1-/- lines, we uncovered the compensatory mechanism for runx1-independent hematopoiesis. We show that, in the absence of a functional runx1, a cd41-green fluorescent protein (GFP)+ population of hematopoietic precursors still emerge from the hemogenic endothelium and can colonize the hematopoietic tissues of the mutant embryos. Single-cell RNA sequencing of the cd41-GFP+ cells identified a set of runx1-/--specific signature genes during hematopoiesis. Significantly, gata2b, which normally acts upstream of runx1 for the generation of HSCs, was increased in the cd41-GFP+ cells in runx1-/- embryos. Interestingly, genetic inactivation of both gata2b and its paralog gata2a did not affect hematopoiesis. However, knocking out runx1 and any 3 of the 4 alleles of gata2a and gata2b abolished definitive hematopoiesis. Gata2 expression was also upregulated in hematopoietic cells in Runx1-/- mice, suggesting the compensatory mechanism is conserved. Our findings indicate that RUNX1 and GATA2 serve redundant roles for HSC production, acting as each other's safeguard.

Indexed as

HemangioblastsAnimalsCore Binding Factor Alpha 2 SubunitGATA2 Transcription FactorHematopoiesisHematopoietic Stem CellsMiceZebrafishZebrafish ProteinsCore Binding Factor Alpha 2 SubunitGata2a protein, zebrafishGata2 protein, mouseGATA2 Transcription FactorRunx1 protein, mouserunx1 protein, zebrafishZebrafish Proteins

Identifiers

PMID34492681
PMCPMC9153008
OpenAlexW3196555874

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.