Evidence map›Paper›PMID 25866967›Full record

ArticleThe Journal of clinical investigation2015

Endothelium and NOTCH specify and amplify aorta-gonad-mesonephros-derived hematopoietic stem cells.

Brandon K Hadland, Barbara Varnum-Finney, Michael G Poulos, Randall T Moon, Jason M Butler, Shahin Rafii, Irwin D Bernstein

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Transition of signal requirement in hematopoietic stem cell development from hemogenic endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Review
  16. Article
  17. The evolving hematopoietic niche during development.Frontiers in molecular biosciences · 2024
    Review
  18. Review
  19. Article
  20. Article

4 more citing papers are in PubMed but not listed here.

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

7 authors at 5 institutions in 2 countries.

Brandon K Hadland
Barbara Varnum-Finney
Michael G Poulos
Randall T Moon
Jason M Butler
Shahin Rafii
Irwin D Bernstein
Fred Hutch Cancer Center · USHoward Hughes Medical Institute · USCornell University · USStem Cell Institute · PAUniversity of Washington · US

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
CAREER DEVELOPMENT IN PEDIATRIC AND MEDICAL ONCOLOGYK12CA076930 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DAVIDSON, NANCY ELLEN, MESHINCHI, SOHEIL · 1997 to 2025
$13.1M
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
PEDIATRIC ONCOLOGY RESEARCH TRAINING PROGRAMT32CA009351 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Elizabeth R Lawlor, SOHEIL MESHINCHI · 1985 to 2026
$7.0M
Howard Hughes Medical InstituteNCI NIH HHS K12 CA076930NCI NIH HHS K12CA076930NCI NIH HHS T32 CA009351NCI NIH HHS T32CA009351NHLBI NIH HHS HL099997NHLBI NIH HHS HL100395NHLBI NIH HHS U01 HL099997NHLBI NIH HHS U01 HL100395
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) first emerge during embryonic development within vessels such as the dorsal aorta of the aorta-gonad-mesonephros (AGM) region, suggesting that signals from the vascular microenvironment are critical for HSC development. Here, we demonstrated that AGM-derived endothelial cells (ECs) engineered to constitutively express AKT (AGM AKT-ECs) can provide an in vitro niche that recapitulates embryonic HSC specification and amplification. Specifically, nonengrafting embryonic precursors, including the VE-cadherin-expressing population that lacks hematopoietic surface markers, cocultured with AGM AKT-ECs specified into long-term, adult-engrafting HSCs, establishing that a vascular niche is sufficient to induce the endothelial-to-HSC transition in vitro. Subsequent to hematopoietic induction, coculture with AGM AKT-ECs also substantially increased the numbers of HSCs derived from VE-cadherin⁺CD45⁺ AGM hematopoietic cells, consistent with a role in supporting further HSC maturation and self-renewal. We also identified conditions that included NOTCH activation with an immobilized NOTCH ligand that were sufficient to amplify AGM-derived HSCs following their specification in the absence of AGM AKT-ECs. Together, these studies begin to define the critical niche components and resident signals required for HSC induction and self-renewal ex vivo, and thus provide insight for development of defined in vitro systems targeted toward HSC generation for therapeutic applications.

Indexed as

AnimalsAntigens, CDAortaCadherin 5CadherinsCells, CulturedColony-Forming Units AssayEndothelial CellsEndothelium, VascularFemaleGonadsGraft SurvivalHematopoietic Stem Cell TransplantationHematopoietic SystemIntracellular Signaling Peptides and ProteinsLeukocyte Common AntigensAntigens, CDCadherin 5Cadherinsdelta proteinIntracellular Signaling Peptides and ProteinsLeukocyte Common AntigensMembrane ProteinsNotch1 protein, mouseNotch2 protein, mousePtprc protein, mouseReceptor, Notch1Receptor, Notch2

Identifiers

PMID25866967
PMCPMC4463208
OpenAlexW2050326153

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.