Evidence map›Paper›PMID 34170284›Full record

ArticleBlood advances2021

Single-cell ATAC-seq reveals GATA2-dependent priming defect in myeloid and a maturation bottleneck in lymphoid lineages.

Serine Avagyan, Margaret C Weber, Sai Ma, Meera Prasad, William P Mannherz, Song Yang, Jason D Buenrostro, Leonard I Zon

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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  4. Article
  5. Review
  6. scBlood: A comprehensive single-cell accessible chromatin database of blood cells.Computational and structural biotechnology journal · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Transgenic IDH2Oncogene · 2023
    Article
  12. The role of GATA2 in adult hematopoiesis and cell fate determination.Frontiers in cell and developmental biology · 2023
    Review
  13. Review
  14. Article
  15. Article
  16. Review
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 2 institutions in 1 country.

Serine AvagyanDana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA.
Margaret C WeberBoston Children's Hospital, Boston, MA.ORCID 0000-0001-7413-1300
Sai MaDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA.
Meera PrasadBoston Children's Hospital, Boston, MA.
William P MannherzBoston Children's Hospital, Boston, MA.ORCID 0000-0003-4472-7394
Song YangBoston Children's Hospital, Boston, MA.
Jason D BuenrostroDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA.
Leonard I ZonBoston Children's Hospital, Boston, MA.ORCID 0000-0003-0860-926X
Boston Children's Hospital · USBroad Institute · US

Funding

Stem cells for therapeutics discovery in genetic blood disordersU01HL134812 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q, LIPTON, JEFFREY M · 2016 to 2022
$8.3M
Molecular Circuits in the Hematopoietic Stem Cell NicheRC2DK120535 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2020 to 2024
$8.2M
Systems Biology of Bone Marrow Failure and MDS for Precision MedicineRC2DK122533 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI FIGUEROA, MARIA EUGENIA, FLEMING, MARK D · 2019 to 2023
$6.4M
Project-002U54DK110805 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ORKIN, STUART H, ZON, LEONARD IRA · 2016 to 2020
$5.9M
Transcriptional response to signaling during hematopoiesisR01HL144780 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI ZON, LEONARD IRA · 2019 to 2022
$2.1M
NHLBI NIH HHS R01 HL144780NHLBI NIH HHS U01 HL134812NIDDK NIH HHS RC2 DK120535NIDDK NIH HHS RC2 DK122533NIDDK NIH HHS U54 DK110805
6 · The paper itself

Abstract

Germline heterozygous mutations in GATA2 are associated with a syndrome characterized by cytopenias, atypical infections, and increased risk of hematologic malignancies. Here, we generated a zebrafish mutant of gata2b that recapitulated the myelomonocytopenia and B-cell lymphopenia of GATA2 deficiency syndrome. Using single-cell assay for transposase accessible chromatin with sequencing of marrow cells, we showed that loss of gata2b led to contrasting alterations in chromosome accessibility in early myeloid and lymphoid progenitors, associated with defects in gene expression. Within the myeloid lineage in gata2b mutant zebrafish, we identified an attenuated myeloid differentiation with reduced transcriptional priming and skewing away from the monocytic program. In contrast, in early lymphoid progenitors, gata2b loss led to accumulation of B-lymphoid transcription factor accessibility coupled with increased expression of the B-cell lineage-specification program. However, gata2b mutant zebrafish had incomplete B-cell lymphopoiesis with loss of lineage-specific transcription factor accessibility in differentiating B cells, in the context of aberrantly reduced oxidative metabolic pathways. Our results establish that transcriptional events in early progenitors driven by Gata2 are required to complete normal differentiation.

Indexed as

Chromatin Immunoprecipitation SequencingGATA2 DeficiencyAnimalsGATA2 Transcription FactorLymphopoiesisTranscription FactorsXenopus ProteinsZebrafishGATA2 protein, XenopusGATA2 Transcription FactorTranscription FactorsXenopus Proteins

Identifiers

PMID34170284
PMCPMC8221101
OpenAlexW3175754962

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.