Evidence map›Paper›PMID 26477526›Full record

ArticleExperimental hematology2016

GSK3β inhibition activates the CDX/HOX pathway and promotes hemogenic endothelial progenitor differentiation from human pluripotent stem cells.

Kenji Kitajima, Marino Nakajima, Mai Kanokoda, Michael Kyba, Abhijit Dandapat, Jakub Tolar, Megumu K Saito, Masashi Toyoda, Akihiro Umezawa, Takahiko Hara

Abstract read
In one paragraph

Article in Experimental hematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Modification of Lhx2 activity forFrontiers in cell and developmental biology · 2024
    Article
  4. GSK3β Inhibition Ameliorates Atherosclerotic Calcification.International journal of molecular sciences · 2023
    Article
  5. GSK3β Inhibition Reduced Vascular Calcification inInternational journal of molecular sciences · 2023
    Article
  6. Wnt regulation of hematopoietic stem cell development and disease.Current topics in developmental biology · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. A Case of Identity:Cancers · 2019
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. The role of Wnt signaling in hematopoietic stem cell development.Critical reviews in biochemistry and molecular biology · 2017
    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

10 authors.

Kenji KitajimaStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address: kitajima-kj@igakuken.or.jp.
Marino NakajimaStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Mai KanokodaStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Michael KybaLillehei Heart Institute, Department of Pediatrics, University of Minnesota, Minneapolis, MN.
Abhijit DandapatLillehei Heart Institute, Department of Pediatrics, University of Minnesota, Minneapolis, MN.
Jakub TolarPediatric Hematology-Oncology, Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN.
Megumu K SaitoClinical Application Department, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Masashi ToyodaResearch Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Akihiro UmezawaDepartment of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, Japan.
Takahiko HaraStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
FSHD iPS Cells: Genetic Correction and MyogenesisR01NS083549 · NINDS · UNIVERSITY OF MINNESOTA · PI KYBA, MICHAEL · 2013 to 2017
$1.7M
NCI NIH HHS P30 CA077598NINDS NIH HHS R01 NS083549
6 · The paper itself

Abstract

WNT/β-CATENIN signaling promotes the hematopoietic/endothelial differentiation of human embryonic stem cells and human induced pluripotent stem cells (hiPSCs). The transient addition of a GSK3β inhibitor (GSKi) has been found to facilitate in vitro endothelial cell differentiation from hESCs/hiPSCs. Because hematopoietic and endothelial cells are derived from common progenitors (hemogenic endothelial progenitors [HEPs]), we examined the effect of transient GSKi treatment on hematopoietic cell differentiation from hiPSCs. We found that transient GSKi treatment at the start of hiPSC differentiation induction altered the gene expression profile of the cells. Multiple CDX/HOX genes, which are expressed in the posterior mesoderm of developing embryos, were significantly upregulated by GSKi treatment. Further, inclusion of the GSKi in a serum- and stroma-free culture with chemically defined medium efficiently induced HEPs, and the HEPs gave rise to various lineages of hematopoietic and endothelial cells. Therefore, transient WNT/β-CATENIN signaling triggers activation of the CDX/HOX pathway, which in turn confers hemogenic posterior mesoderm identity to differentiating hiPSCs. These data enhance our understanding of human embryonic hematopoietic/endothelial cell development and provide a novel in vitro system for inducing the differentiation of hematopoietic cells from hiPSCs.

Indexed as

Genes, HomeoboxCell DifferentiationEnzyme InhibitorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansPluripotent Stem CellsEnzyme InhibitorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, human

Identifiers

PMID26477526
PMCPMC5160023

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Registered trials

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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.