Evidence map›Paper›PMID 32499402›Full record

ArticleGenes & development2020

Transcriptional regulatory network controlling the ontogeny of hematopoietic stem cells.

Peng Gao, Changya Chen, Elizabeth D Howell, Yan Li, Joanna Tober, Yasin Uzun, Bing He, Long Gao, Qin Zhu, Arndt F Siekmann and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed, 48 citations in OpenAlex.

  1. Trial
  2. Article
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  4. Jund orchestratesProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Multimodal analysis ofbioRxiv : the preprint server for biology · 2025
    Article
  6. ABlood vessels, thrombosis & hemostasis · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Review
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  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Hematopoietic Stem Cell Development in Mammalian Embryos.Advances in experimental medicine and biology · 2023
    Review
  18. Review
  19. Article
  20. 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

12 authors at 3 institutions in 1 country.

Peng Gao *Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Changya Chen *Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Elizabeth D Howell *Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Yan LiDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Joanna ToberDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Yasin UzunDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Bing HeDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Long GaoDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Qin ZhuGraduate Group in Genomics and Computational Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Arndt F SiekmannDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nancy A SpeckDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Kai TanDivision of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.ORCID 0000-0002-9104-5567
University of Pennsylvania · USChildren's Hospital of Philadelphia · USCancer Research Institute · US

Funding

Biochemistry of Leukemia Virus Core-Binding FactorR01HL091724 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SPECK, NANCY · 2008 to 2024
$8.3M
Graduate Training in Developmental BiologyT32HD083185 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael Granato, Foteini Mourkioti · 2015 to 2026
$4.0M
Mechanisms of endothelial-to-hemogenic transition mediated by Runx1R01HD089245 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI SPECK, NANCY, TAN, KAI · 2017 to 2021
$2.1M
EPIGENETIC REGULATION OF STEM CELL FATE CHOICER01HG006130 · NHGRI · UNIVERSITY OF IOWA · PI TAN, KAI · 2012 to 2016
$1.7M
Computational Methods for Unraveling Combinatorial Gene RegulationR01GM108716 · NIGMS · UNIVERSITY OF IOWA · PI TAN, KAI · 2014 to 2017
$1.2M
A TOOLKIT FOR IDENTIFYING CAUSAL VARIANTS IN TRANSCRIPTIONAL ENHANCERSR01GM104369 · NIGMS · UNIVERSITY OF IOWA · PI TAN, KAI · 2014 to 2017
$1.2M
Identifying necessary chromatin states and targets for hemogenic specification and reprogrammingF31HL150952 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI HOWELL, ELIZABETH · 2020 to 2021
$70k
NHGRI NIH HHS R01 HG006130NHLBI NIH HHS F31 HL150952NHLBI NIH HHS R01 HL091724NICHD NIH HHS R01 HD089245NICHD NIH HHS T32 HD083185NIGMS NIH HHS R01 GM104369NIGMS NIH HHS R01 GM108716
6 · The paper itself

Abstract

Hematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-seq and histone mark ChIP-seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in mice. The five populations analyzed were embryonic day 10.5 (E10.5) endothelium and hemogenic endothelium from the major arteries, an enriched population of prehematopoietic stem cells (pre-HSCs), fetal liver HSCs, and adult bone marrow HSCs. Using epigenetic signatures, we identified enhancers for each developmental stage. Only 12% of enhancers are primed, and 78% are active, suggesting the vast majority of enhancers are established de novo without prior priming in earlier stages. We constructed developmental stage-specific transcriptional regulatory networks by linking enhancers and predicted bound transcription factors to their target promoters using a novel computational algorithm, target inference via physical connection (TIPC). TIPC predicted known transcriptional regulators for the endothelial-to-hematopoietic transition, validating our overall approach, and identified putative novel transcription factors, including the broadly expressed transcription factors SP3 and MAZ. Finally, we validated a role for SP3 and MAZ in the formation of hemogenic endothelium. Our data and computational analyses provide a useful resource for uncovering regulators of HSC formation.

Indexed as

AlgorithmsAnimalsDNA-Binding ProteinsEnhancer Elements, GeneticEpigenesis, GeneticGene EditingGene Expression Regulation, DevelopmentalGene Regulatory NetworksHematopoiesisHematopoietic Stem CellsMiceSp3 Transcription FactorTranscription FactorsTranscriptomec-MYC-associated zinc finger proteinDNA-Binding ProteinsSp3 protein, mouseSp3 Transcription FactorTranscription Factorsembryonic hematopoiesisenhancerepigeneticshemogenic endotheliumHSCregulatory network

Identifiers

PMID32499402
PMCPMC7328518
OpenAlexW3033732631

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.