Evidence map›Paper›PMID 34675061›Full record

ArticleGenes & development2021

Efficient hemogenic endothelial cell specification by RUNX1 is dependent on baseline chromatin accessibility of RUNX1-regulated TGFβ target genes.

Elizabeth D Howell, Amanda D Yzaguirre, Peng Gao, Raphael Lis, Bing He, Melike Lakadamyali, Shahin Rafii, Kai Tan, Nancy A Speck

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed, 35 citations in OpenAlex.

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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

9 authors at 4 institutions in 1 country.

Elizabeth D HowellAbramson Family Cancer Research Institute, Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania 19104, USA.ORCID 0000-0001-6079-0700
Amanda D YzaguirreAbramson Family Cancer Research Institute, Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania 19104, USA.ORCID 0000-0002-7346-1102
Peng GaoDepartment of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Raphael LisAnsary Stem Cell Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.ORCID 0000-0003-2541-4798
Bing HeDepartment of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.ORCID 0000-0002-8797-7919
Melike LakadamyaliDepartment of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania 19104, USA.ORCID 0000-0002-7524-6414
Shahin RafiiAnsary Stem Cell Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.ORCID 0000-0001-5605-1067
Kai TanDepartment of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.ORCID 0000-0002-9104-5567
Nancy A SpeckAbramson Family Cancer Research Institute, Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania 19104, USA.ORCID 0000-0002-1893-582X
Cancer Research Institute · USChildren's Hospital of Philadelphia · USHoward Hughes Medical Institute · USUniversity of Pennsylvania · US

Funding

IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
Biochemistry of Leukemia Virus Core-Binding FactorR01HL091724 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SPECK, NANCY · 2008 to 2024
$8.3M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
HEMATOPOIESIS TRAINING GRANTT32DK007780 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI TONG, WEI · 1999 to 2023
$6.7M
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
Ectopic Runx1 expression in non-hemogenic endothelium induces blood formationF31HL120615 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI PHILLIPS, AMANDA DANIELLE · 2013 to 2015
$108k
Identifying necessary chromatin states and targets for hemogenic specification and reprogrammingF31HL150952 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI HOWELL, ELIZABETH · 2020 to 2021
$70k
NCI NIH HHS T32 CA009140NHLBI NIH HHS F31 HL120615NHLBI NIH HHS F31 HL150952NHLBI NIH HHS R01 HL091724NHLBI NIH HHS U01 HL100405NICHD NIH HHS R01 HD089245NICHD NIH HHS T32 HD083185NIDDK NIH HHS T32 DK007780
6 · The paper itself

Abstract

Hematopoietic stem and progenitor cells (HSPCs) are generated de novo in the embryo from hemogenic endothelial cells (HECs) via an endothelial-to-hematopoietic transition (EHT) that requires the transcription factor RUNX1. Ectopic expression of RUNX1 alone can efficiently promote EHT and HSPC formation from embryonic endothelial cells (ECs), but less efficiently from fetal or adult ECs. Efficiency correlated with baseline accessibility of TGFβ-related genes associated with endothelial-to-mesenchymal transition (EndoMT) and participation of AP-1 and SMAD2/3 to initiate further chromatin remodeling along with RUNX1 at these sites. Activation of TGFβ signaling improved the efficiency with which RUNX1 specified fetal ECs as HECs. Thus, the ability of RUNX1 to promote EHT depends on its ability to recruit the TGFβ signaling effectors AP-1 and SMAD2/3, which in turn is determined by the changing chromatin landscape in embryonic versus fetal ECs. This work provides insight into regulation of EndoMT and EHT that will guide reprogramming efforts for clinical applications.

Indexed as

HemangioblastsCell DifferentiationChromatinCore Binding Factor Alpha 2 SubunitFetusHematopoiesisHematopoietic Stem CellsHumansTransforming Growth Factor betaTransforming Growth Factor beta1ChromatinCore Binding Factor Alpha 2 SubunitRUNX1 protein, humanTransforming Growth Factor betaTransforming Growth Factor beta1endothelial-to-hematopoietic transitionendothelial-to-mesenchymal transitionhematopoiesishemogenic endotheliumRUNX1TGFβ

Identifiers

PMID34675061
PMCPMC8559682
OpenAlexW3207189600

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.