Evidence map›Paper›PMID 16682494›Full record

ArticleThe Journal of experimental medicine2006

RARgamma is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation.

Louise E Purton, Sebastian Dworkin, Gemma Haines Olsen, Carl R Walkley, Stewart A Fabb, Steven J Collins, Pierre Chambon

Erratum issuedOpen access · bronzeAbstract readComparative Study
In one paragraph

Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

117 citing papers in PubMed, 193 citations in OpenAlex.

  1. Review
  2. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. Review
  5. The Influences of RARγ on the Behavior of Normal and Cancer Stem Cells.International journal of molecular sciences · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Deregulation of All-International journal of molecular sciences · 2023
    Review
  13. Targeting the Retinoic Acid Pathway to Eradicate Cancer Stem Cells.International journal of molecular sciences · 2023
    Review
  14. Review
  15. Osteoblast Lineage Support of Hematopoiesis in Health and Disease.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Review
  16. Article
  17. Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells.International journal of molecular sciences · 2022
    Review
  18. Oncogenes and the Origins of Leukemias.International journal of molecular sciences · 2022
    Review
  19. Put in a "CaCells · 2022
    Review
  20. Article

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

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Louise E PurtonTrescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. lpurton@partners.org
Sebastian Dworkin
Gemma Haines Olsen
Carl R Walkley
Stewart A Fabb
Steven J Collins
Pierre Chambon
Peter MacCallum Cancer Centre · AUCollège de France · FRFred Hutch Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) sustain lifelong production of all blood cell types through finely balanced divisions leading to self-renewal and differentiation. Although several genes influencing HSC self-renewal have been identified, to date no gene has been described that, when activated, enhances HSC self-renewal and, when inactivated [corrected] promotes HSC differentiation. We observe that the retinoic acid receptor (RAR)gamma is selectively expressed in primitive hematopoietic precursors and that the bone marrow of RARgamma knockout mice exhibit markedly reduced numbers of HSCs associated with increased numbers of more mature progenitor cells compared with wild-type mice. In contrast, RARalpha is widely expressed in hematopoietic cells, but RARalpha knockout mice do not exhibit any HSC or progenitor abnormalities. Primitive hematopoietic precursors overexpressing RARalpha differentiate predominantly to granulocytes in short-term culture, whereas those overexpressing RARgamma exhibit a much more undifferentiated phenotype. Furthermore, loss of RARgamma abrogated the potentiating effects of all-trans retinoic acid on the maintenance of HSCs in ex vivo culture. Finally, pharmacological activation of RARgamma ex vivo promotes HSC self-renewal, as demonstrated by serial transplant studies. We conclude that the RARs have distinct roles in hematopoiesis and that RARgamma is a critical physiological and pharmacological regulator of the balance between HSC self-renewal and differentiation.

Indexed as

Cell ProliferationAnimalsAntineoplastic AgentsBone MarrowCell DifferentiationCells, CulturedGene Expression RegulationGranulocytesHematopoiesisHematopoietic Stem CellsHematopoietic Stem Cell TransplantationMiceReceptors, Retinoic AcidRetinoic Acid Receptor gammaTretinoinAntineoplastic AgentsReceptors, Retinoic AcidRetinoic Acid Receptor gammaTretinoin

Identifiers

PMID16682494
PMCPMC2121209
OpenAlexW2150054925

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.