Evidence map›Paper›PMID 16480521›Full record

ArticleJournal of translational medicine2006

The thrombopoietin receptor, c-Mpl, is a selective surface marker for human hematopoietic stem cells.

John M Ninos, Leigh C Jefferies, Christopher R Cogle, William G Kerr

Abstract read
In one paragraph

Article in Journal of translational medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Cell Lineage Affiliation During Hematopoiesis.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Hematopoietic stem cells and extramedullary hematopoiesis in the lungs.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Modeling the Hematopoietic Landscape.Frontiers in cell and developmental biology · 2019
    Review
  19. Article
  20. Article
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

4 authors.

John M NinosH, Lee Moffitt Cancer Center and Research Institute, Immunology Program, Department of Interdisciplinary Oncology, University of South Florida, SRB-2, 12902 Magnolia Drive, Tampa, FL 33612-9416, USA. ninosj@moffitt.usf.edu
Leigh C Jefferies
Christopher R Cogle
William G Kerr

Funding

IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
SCID HU MODEL FOR HIV INFECTION OF THE CNSP01NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 1989 to 2007
$8.2M
Role of SHIP in NK Cell BiologyR01HL072523 · NHLBI · UPSTATE MEDICAL UNIVERSITY · PI KERR, WILLIAM GARROW · 2002 to 2014
$4.3M
TRANSFUSION MEDICINE RESEARCH TRAINING PROGRAMT32HL007775 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SIEGEL, DONALD LAWRENCE · 1993 to 2023
$2.8M
Peer-Led Problem-Solving Intervention for Family CaregiversR21AG044333 · NIA · UNIVERSITY OF ALABAMA IN TUSCALOOSA · PI PARMELEE, PATRICIA A. · 2015 to 2016
$388k
NCI NIH HHS T32 CA009140NHLBI NIH HHS R01 HL072523NHLBI NIH HHS T32 HL007775NIA NIH HHS R21 AG044333NINDS NIH HHS P01 NS027405
6 · The paper itself

Abstract

backgroundThrombopoietin (TPO), the primary cytokine regulating megakaryocyte proliferation and differentiation, exerts significant influence on other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages. We previously demonstrated that the receptor for TPO, c-mpl, is expressed by a subset of human adult bone marrow hematopoietic stem/progenitor cells (HSC/PC) that are enriched for long-term multilineage repopulating ability in the SCID-hu Bone in vivo model of human hematopoiesis.

methodsHere, we employ flow cytometry and an anti-c-mpl monoclonal antibody to comprehensively define the surface expression pattern of c-mpl in four differentiation stages of human CD34+ HSC/PC (I: CD34+38--, II: CD34+38dim, III: CD34+38+, IV: CD34dim38+) for the major sources of human HSC: fetal liver (FL), umbilical cord blood (UCB), adult bone marrow (ABM), and cytokine-mobilized peripheral blood stem cells (mPBSC). We use a surrogate in vivo model of human thymopoiesis, SCID-hu Thy/Liv, to compare the capacity of c-mpl+ vs. c-mpl-- CD34+38--/dim HSC/PC for thymocyte reconstitution.

resultsFor all tissue sources, the percentage of c-mpl+ cells was significantly highest in stage I HSC/PC (FL 72 +/- 10%, UCB 67 +/- 19%, ABM 82 +/- 16%, mPBSC 71 +/- 15%), and decreased significantly through stages II, III, and IV ((FL 3 +/- 3%, UCB 8 +/- 13%, ABM 0.6 +/- 0.6%, mPBSC 0.2 +/- 0.1%) [ANOVA: P < 0.0001]. The relative median fluorescence intensity of c-mpl expression was similarly highest in stage I, decreasing through stage IV [ANOVA: P < 0.0001]. No significant differences between tissue sources were observed for either % c-mpl+ cells [P = 0.89] or intensity of c-mpl expression [P = 0.21]. Primary Thy/Liv grafts injected with CD34+38--/dimc-mpl+ cells showed slightly higher levels of donor HLA+ thymocyte reconstitution vs. CD34+38--/dimc-mpl---injected grafts and non-injected controls (c-mpl+ vs. c-mpl--: CD2+ 6.8 +/- 4.5% vs. 2.8 +/- 3.3%, CD4+8-- 54 +/- 35% vs. 31 +/- 29%, CD4--8+ 29 +/- 19% vs. 18 +/- 14%).

conclusionThese findings support the hypothesis that the TPO receptor, c-mpl, participates in the regulation of primitive human HSC from mid-fetal through adult life. This study extends our previous work documenting human B-lineage, myeloid and CD34+ cell repopulation by c-mpl+ progenitors to show that c-mpl+ HSC/PC are also capable of significant T-lineage reconstitution in vivo. These results suggest that c-mpl merits consideration as a selective surface marker for the identification and isolation of human HSC in both basic research and clinical settings.

Identifiers

PMID16480521
PMCPMC1402332

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.