Evidence map›Paper›PMID 27132889›Full record

ArticleStem cell reports2016

A Multi-Lineage Screen Reveals mTORC1 Inhibition Enhances Human Pluripotent Stem Cell Mesendoderm and Blood Progenitor Production.

Emanuel Joseph Paul Nazareth, Nafees Rahman, Ting Yin, Peter William Zandstra

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Trends and targets of various types of stem cell derived transfusable RBC substitution therapy: Obstacles that need to be converted to opportunity.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2020
    Review
  8. PI3K in stemness regulation: from development to cancer.Biochemical Society transactions · 2020
    Review
  9. Article
  10. Article
  11. Role of mTOR Signaling in Female Reproduction.Frontiers in endocrinology · 2019
    Review
  12. Article
  13. Review
  14. Teratogen screening with human pluripotent stem cells.Integrative biology : quantitative biosciences from nano to macro · 2018
    Review
  15. Article
  16. mTOR signaling in stem and progenitor cells.Development (Cambridge, England) · 2018
    Review
  17. Article
  18. Article
  19. 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 at 1 institution in 1 country.

Emanuel Joseph Paul NazarethInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Nafees RahmanInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada.
Ting YinInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Peter William ZandstraInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada; Medicine by Design, University of Toronto, Toronto, ON M5S 3G9, Canada. Electronic address: peter.zandstra@utoronto.ca.
University of Toronto · CA

Funding

CIHR
6 · The paper itself

Abstract

Human pluripotent stem cells (hPSCs) exist in heterogeneous micro-environments with multiple subpopulations, convoluting fate-regulation analysis. We patterned hPSCs into engineered micro-environments and screened responses to 400 small-molecule kinase inhibitors, measuring yield and purity outputs of undifferentiated, neuroectoderm, mesendoderm, and extra-embryonic populations. Enrichment analysis revealed mammalian target of rapamycin (mTOR) inhibition as a strong inducer of mesendoderm. Dose responses of mTOR inhibitors such as rapamycin synergized with Bone Morphogenetic protein 4 (BMP4) and activin A to enhance the yield and purity of BRACHYURY-expressing cells. Mechanistically, small interfering RNA knockdown of RAPTOR, a component of mTOR complex 1, phenocopied the mesendoderm-enhancing effects of rapamycin. Functional analysis during mesoderm and endoderm differentiation revealed that mTOR inhibition increased the output of hemogenic endothelial cells 3-fold, with a concomitant enhancement of blood colony-forming cells. These data demonstrate the power of our multi-lineage screening approach and identify mTOR signaling as a node in hPSC differentiation to mesendoderm and its derivatives.

Indexed as

ActivinsBone Morphogenetic Protein 4Brachyury ProteinCell DifferentiationCell LineageCellular MicroenvironmentEndodermEnzyme InhibitorsFetal ProteinsGene Expression Regulation, DevelopmentalHumansMechanistic Target of Rapamycin Complex 1Neural PlatePhosphotransferasesPluripotent Stem CellsRegulatory-Associated Protein of mTORactivin AActivinsBMP4 protein, humanBone Morphogenetic Protein 4Brachyury ProteinEnzyme InhibitorsFetal ProteinsMechanistic Target of Rapamycin Complex 1PhosphotransferasesRegulatory-Associated Protein of mTORSirolimusSmall Molecule LibrariesT-Box Domain Proteins

Identifiers

PMID27132889
PMCPMC4939733
OpenAlexW2345125968

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.