Evidence map›Paper›PMID 21170035›Full record

ArticleNature cell biology2011

HoxA3 is an apical regulator of haemogenic endothelium.

Michelina Iacovino, Diana Chong, Istvan Szatmari, Lynn Hartweck, Danielle Rux, Arianna Caprioli, Ondine Cleaver, Michael Kyba

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

46 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Biomolecules · 2022
    Article
  7. Article
  8. Article
  9. Biomechanical cues as master regulators of hematopoietic stem cell fate.Cellular and molecular life sciences : CMLS · 2021
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. The Role of Runx1 in Embryonic Blood Cell Formation.Advances in experimental medicine and biology · 2017
    Review
  20. 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 4 institutions in 1 country.

Michelina IacovinoLillehei Heart Institute and Department of Pediatrics, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455, USA.
Diana Chong
Istvan Szatmari
Lynn Hartweck
Danielle Rux
Arianna Caprioli
Ondine Cleaver
Michael Kyba
University of Minnesota · USThe University of Texas Southwestern Medical Center · USMinneapolis Heart Institute Foundation · USSouthwestern Medical Center

Funding

Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
Midwestern Progenitor Cell ConsortiumU01HL100407 · NHLBI · UNIVERSITY OF MINNESOTA · PI GARRY, DANIEL J., KYBA, MICHAEL · 2009 to 2015
$7.8M
Probing the Hematopoietic Hox CodeR01HL081186 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI KYBA, MICHAEL · 2007 to 2011
$2.1M
NHLBI NIH HHS 1R01HL081186-01NHLBI NIH HHS R01 HL081186NHLBI NIH HHS U01 HL100407NIDCR NIH HHS T32 DE007057
6 · The paper itself

Abstract

During development, haemogenesis occurs invariably at sites of vasculogenesis. Between embryonic day (E) 9.5 and E10.5 in mice, endothelial cells in the caudal part of the dorsal aorta generate haematopoietic stem cells and are referred to as haemogenic endothelium. The mechanisms by which haematopoiesis is restricted to this domain, and how the morphological transformation from endothelial to haematopoietic is controlled are unknown. We show here that HoxA3, a gene uniquely expressed in the embryonic but not yolk sac vasculature, restrains haematopoietic differentiation of the earliest endothelial progenitors, and induces reversion of the earliest haematopoietic progenitors into CD41-negative endothelial cells. This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1. Through loss-of-function, and gain-of-function epistasis experiments, and the identification of antipodally regulated targets, we show that among these factors, Runx1 is uniquely able to erase the endothelial program set up by HoxA3. These results suggest both why a frank endothelium does not precede haematopoiesis in the yolk sac, and why haematopoietic stem cell generation requires Runx1 expression only in endothelial cells.

Indexed as

HematopoiesisAnimalsBase SequenceCell DifferentiationCell LineageCore Binding Factor Alpha 2 SubunitEmbryo, MammalianFlow CytometryGene Expression ProfilingGene Expression Regulation, DevelopmentalHemangioblastsHomeodomain ProteinsIn Situ HybridizationMesodermMiceMice, KnockoutCore Binding Factor Alpha 2 SubunitHomeodomain ProteinsHoxa3 protein, mouseRunx1 protein, mouse

Identifiers

PMID21170035
PMCPMC3079247
OpenAlexW2012204251

What OpenQuestion holds

Textmetadata
LicenceTDM
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.