Evidence map›Paper›PMID 24637115›Full record

ArticleGenes & development2014

The Notch1 transcriptional activation domain is required for development and reveals a novel role for Notch1 signaling in fetal hematopoietic stem cells.

Dawson M Gerhardt, Kostandin V Pajcini, Teresa D'altri, Lili Tu, Rajan Jain, Lanwei Xu, Michael J Chen, Stacey Rentschler, Olga Shestova, Gerald B Wertheim and 9 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2014. 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, 64 citations in OpenAlex.

  1. Review
  2. Notch NICD domains form biomolecular condensates.Journal of cell communication and signaling · 2025
    Article
  3. Review
  4. The evolving hematopoietic niche during development.Frontiers in molecular biosciences · 2024
    Review
  5. Article
  6. Article
  7. The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer.ACS pharmacology & translational science · 2023
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
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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

19 authors at 7 institutions in 2 countries.

Dawson M GerhardtAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Kostandin V Pajcini
Teresa D'altri
Lili Tu
Rajan Jain
Lanwei Xu
Michael J Chen
Stacey Rentschler
Olga Shestova
Gerald B Wertheim
John W Tobias
Michael Kluk
Antony W Wood
Jon C Aster
Phyllis A Gimotty
Jonathan A Epstein
Nancy Speck
Anna Bigas
Warren S Pear
University of Pennsylvania · USCancer Research Institute · USUPMC Hillman Cancer Center · USHospital del Mar Research Institute · ESBrigham and Women's Hospital · USCell Signaling Technology (United States) · USHarvard University · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
Training Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0M
Protein CoreP01CA119070 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ASTER, JON C. · 2006 to 2016
$10.3M
Expansion of Cardiac and Hematopoietic Pregenitors by Wnt and NotchU01HL100395 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D, MOON, RANDALL TODD · 2009 to 2015
$8.4M
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
Notch Regulation of Hematopoietic Cell FatesR01AI047833 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI JORDAN, MARTHA S, PEAR, WARREN S · 2000 to 2022
$7.4M
Research BaseP30DK090969 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI CARROLL, MARTIN · 2010 to 2015
$5.7M
Investigating the role of Hopx in cardiac progenitor proliferationK08HL119553 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN · 2013 to 2017
$741k
The Role of Notch Signaling in ArrhythmogenesisK08HL107449 · NHLBI · WASHINGTON UNIVERSITY · PI RENTSCHLER, STACEY LYNN · 2011 to 2015
$660k
NCI NIH HHS P01 CA119070NCI NIH HHS P01CA119070NCI NIH HHS P30 CA016520NCI NIH HHS T32 CA009140NCI NIH HHS T32CA009140NHLBI NIH HHS K08 HL107449NHLBI NIH HHS K08 HL119553NHLBI NIH HHS L40 HL115656NHLBI NIH HHS R01 HL091724NHLBI NIH HHS T32 HL007843NHLBI NIH HHS T32HL007843NHLBI NIH HHS U01 HL100395NHLBI NIH HHS U01 HL100405NHLBI NIH HHS U01HL100405NIAID NIH HHS R01 AI047833NIAID NIH HHS R01AI047833NIDDK NIH HHS P30 DK090969NIGMS NIH HHS T32 GM007229NIGMS NIH HHS T32GM007229
6 · The paper itself

Abstract

Notch1 is required to generate the earliest embryonic hematopoietic stem cells (HSCs); however since Notch-deficient embryos die early in gestation, additional functions for Notch in embryonic HSC biology have not been described. We used two complementary genetic models to address this important biological question. Unlike Notch1-deficient mice, mice lacking the conserved Notch1 transcriptional activation domain (TAD) show attenuated Notch1 function in vivo and survive until late gestation, succumbing to multiple cardiac abnormalities. Notch1 TAD-deficient HSCs emerge and successfully migrate to the fetal liver but are decreased in frequency by embryonic day 14.5. In addition, TAD-deficient fetal liver HSCs fail to compete with wild-type HSCs in bone marrow transplant experiments. This phenotype is independently recapitulated by conditional knockout of Rbpj, a core Notch pathway component. In vitro analysis of Notch1 TAD-deficient cells shows that the Notch1 TAD is important to properly assemble the Notch1/Rbpj/Maml trimolecular transcription complex. Together, these studies reveal an essential role for the Notch1 TAD in fetal development and identify important cell-autonomous functions for Notch1 signaling in fetal HSC homeostasis.

Indexed as

Gene Expression Regulation, DevelopmentalSignal TransductionAnimalsCell LineFetal Stem CellsGene Knock-In TechniquesGene Knockout TechniquesHematopoietic Stem CellsImmunoglobulin J Recombination Signal Sequence-Binding ProteinMiceMutationProtein Structure, TertiaryReceptor, Notch1Survival AnalysisImmunoglobulin J Recombination Signal Sequence-Binding ProteinRbpj protein, mouseReceptor, Notch1hematopoietic stem cellNotchtranscriptional activation domain

Identifiers

PMID24637115
PMCPMC3967047
OpenAlexW2170077318

What OpenQuestion holds

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Registered trials

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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.