Evidence map›Paper›PMID 25418728›Full record

ArticleStem cell reports2014

A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells.

Philip A Beer, David J H F Knapp, Nagarajan Kannan, Paul H Miller, Sonja Babovic, Elizabeth Bulaeva, Nima Aghaeepour, Gabrielle Rabu, Shabnam Rostamirad, Kingsley Shih and 2 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Single-cell analysis identifies a CD33Nature cell biology · 2018
    Article
  8. Article
  9. Review
  10. Article
  11. [Generation of engraftable hematopoietic stem cells from human pluripotent stem cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2017
    Article
  12. Article
  13. 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

12 authors at 2 institutions in 1 country.

Philip A BeerTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
David J H F KnappTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Nagarajan KannanTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Paul H MillerTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Sonja BabovicTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Elizabeth BulaevaTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Nima AghaeepourTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Gabrielle RabuTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Shabnam RostamiradTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Kingsley ShihTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Lisa WeiTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Connie J EavesTerry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC V5Z 1L3, Canada. Electronic address: ceaves@bccrc.ca.
BC Cancer Agency · CAUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Disrupted IKAROS activity is a recurrent feature of some human leukemias, but effects on normal human hematopoietic cells are largely unknown. Here, we used lentivirally mediated expression of a dominant-negative isoform of IKAROS (IK6) to block normal IKAROS activity in primitive human cord blood cells and their progeny. This produced a marked (10-fold) increase in serially transplantable multipotent IK6(+) cells as well as increased outputs of normally differentiating B cells and granulocytes in transplanted immunodeficient mice, without producing leukemia. Accompanying T/natural killer (NK) cell outputs were unaltered, and erythroid and platelet production was reduced. Mechanistically, IK6 specifically increased human granulopoietic progenitor sensitivity to two growth factors and activated CREB and its targets (c-FOS and Cyclin B1). In more primitive human cells, IK6 prematurely initiated a B cell transcriptional program without affecting the hematopoietic stem cell-associated gene expression profile. Some of these effects were species specific, thus identifying novel roles of IKAROS in regulating normal human hematopoietic cells.

Indexed as

Cell ProliferationAnimalsBlotting, WesternB-LymphocytesCell DifferentiationCells, CulturedFetal BloodGene Expression ProfilingGranulocytesHeLa CellsHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansIkaros Transcription FactorInterleukin Receptor Common gamma SubunitMice, Inbred C57BLIkaros 6 protein, humanIkaros Transcription FactorIl2rg protein, mouseInterleukin Receptor Common gamma SubunitProtein Isoforms

Identifiers

PMID25418728
PMCPMC4235152
OpenAlexW1991656443

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.