Evidence map›Paper›PMID 30208304›Full record

ArticleStem cell reports2018

Analysis of Runx1 Using Induced Gene Ablation Reveals Its Essential Role in Pre-liver HSC Development and Limitations of an In Vivo Approach.

Jordi Senserrich, Antoniana Batsivari, Stanislav Rybtsov, Sabrina Gordon-Keylock, Celine Souilhol, Frank Buchholz, David Hills, Suling Zhao, Alexander Medvinsky

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. A Bird's Eye View on the Origin of Aortic Hemogenic Endothelial Cells.Frontiers in cell and developmental biology · 2020
    Article
  7. 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

9 authors at 3 institutions in 2 countries.

Jordi SenserrichMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Antoniana BatsivariMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Stanislav RybtsovMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Sabrina Gordon-KeylockMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Celine SouilholMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Frank BuchholzMax Planck Institute of Molecular Cell Biology and Genetics, Technische Universität Dresden, Dresden 01307, Germany.
David HillsMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Suling ZhaoMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Alexander MedvinskyMRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK. Electronic address: a.medvinsky@ed.ac.uk.
University of Edinburgh · GBMRC Centre for Regenerative Medicine · GBMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

Medical Research Council G0500950Medical Research Council G0900962Medical Research Council MR/K017047/1Medical Research Council MR/L018160/1
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) develop in the embryonic aorta-gonad-mesonephros (AGM) region and subsequently relocate to fetal liver. Runx1 transcription factor is essential for HSC development, but is largely dispensable for adult HSCs. Here, we studied tamoxifen-inducible Runx1 inactivation in vivo. Induction at pre-liver stages (up to embryonic day 10.5) reduced erythromyeloid progenitor numbers, but surprisingly did not block the appearance of Runx1-null HSCs in liver. By contrast, ex vivo analysis showed an absolute Runx1 dependency of HSC development in the AGM region. We found that, contrary to current beliefs, significant Cre-inducing tamoxifen activity persists in mouse blood for at least 72 hr after injection. This deferred recombination can hit healthy HSCs, which escaped early Runx1 ablation and result in appearance of Runx1-null HSCs in liver. Such extended recombination activity in vivo is a potential source of misinterpretation, particularly in analysis of dynamic developmental processes during embryogenesis.

Indexed as

AnimalsAortaCore Binding Factor Alpha 2 SubunitFemaleGene DeletionHematopoiesisHematopoietic Stem CellsLiverMesonephrosMice, Inbred C57BLMice, TransgenicCore Binding Factor Alpha 2 SubunitRunx1 protein, mouseAGMconditional knockoutdevelopmenthematopoiesishematopoietic stem cellsRunx1tamoxifen

Identifiers

PMID30208304
PMCPMC6135942
OpenAlexW2891373637

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.