Evidence map›Paper›PMID 24446491›Full record

ArticleThe Journal of experimental medicine2014

High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias.

Joseph Y Shin, Wenhuo Hu, Mayumi Naramura, Christopher Y Park

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed
11.6field-weighted citation impact, top 1% 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

148 citing papers in PubMed, 238 citations in OpenAlex.

  1. Article
  2. Article
  3. Haematologica · 2026
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  5. Review
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  12. A germlineScience advances · 2025
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  14. Review
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  16. Article
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  18. Article
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  20. Article

88 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

4 authors at 2 institutions in 1 country.

Joseph Y ShinHuman Oncology and Pathogenesis Program and 2 Department of Pathology and 3 Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
Wenhuo Hu
Mayumi Naramura
Christopher Y Park
Memorial Sloan Kettering Cancer Center · USUniversity of Nebraska Medical Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) are heterogeneous with respect to their self-renewal, lineage, and reconstitution potentials. Although c-Kit is required for HSC function, gain and loss-of-function c-Kit mutants suggest that even small changes in c-Kit signaling profoundly affect HSC function. Herein, we demonstrate that even the most rigorously defined HSCs can be separated into functionally distinct subsets based on c-Kit activity. Functional and transcriptome studies show HSCs with low levels of surface c-Kit expression (c-Kit(lo)) and signaling exhibit enhanced self-renewal and long-term reconstitution potential compared with c-Kit(hi) HSCs. Furthermore, c-Kit(lo) and c-Kit(hi) HSCs are hierarchically organized, with c-Kit(hi) HSCs arising from c-Kit(lo) HSCs. In addition, whereas c-Kit(hi) HSCs give rise to long-term lymphomyeloid grafts, they exhibit an intrinsic megakaryocytic lineage bias. These functional differences between c-Kit(lo) and c-Kit(hi) HSCs persist even under conditions of stress hematopoiesis induced by 5-fluorouracil. Finally, our studies show that the transition from c-Kit(lo) to c-Kit(hi) HSC is negatively regulated by c-Cbl. Overall, these studies demonstrate that HSCs exhibiting enhanced self-renewal potential can be isolated based on c-Kit expression during both steady state and stress hematopoiesis. Moreover, they provide further evidence that the intrinsic functional heterogeneity previously described for HSCs extends to the megakaryocytic lineage.

Indexed as

AnimalsCell LineageCell ProliferationColony-Forming Units AssayFluorouracilGene Expression ProfilingHematopoiesisHematopoietic Stem CellsHematopoietic Stem Cell TransplantationMegakaryocytesMiceMice, Inbred C57BLMice, TransgenicProto-Oncogene Proteins c-kitThrombopoiesisFluorouracilProto-Oncogene Proteins c-kit

Identifiers

PMID24446491
PMCPMC3920569
OpenAlexW2147407331

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.