Evidence map›Paper›PMID 27117782›Full record

ArticleStem cell reports2016

Cyclic AMP Signaling through Epac Axis Modulates Human Hemogenic Endothelium and Enhances Hematopoietic Cell Generation.

Shobhit Saxena, Roger E Rönn, Carolina Guibentif, Roksana Moraghebi, Niels-Bjarne Woods

Abstract 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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Functional characterization of human pluripotent stem cell-derived arterial endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2017
    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

5 authors.

Shobhit SaxenaDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
Roger E RönnDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
Carolina GuibentifDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
Roksana MoraghebiDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
Niels-Bjarne WoodsDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden. Electronic address: niels-bjarne.woods@med.lu.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hematopoietic cells emerge from hemogenic endothelium in the developing embryo. Mechanisms behind human hematopoietic stem and progenitor cell development remain unclear. Using a human pluripotent stem cell differentiation model, we report that cyclic AMP (cAMP) induction dramatically increases HSC-like cell frequencies. We show that hematopoietic cell generation requires cAMP signaling through the Exchange proteins activated by cAMP (cAMP-Epac) axis; Epac signaling inhibition decreased both hemogenic and non-hemogenic endothelium, and abrogated hematopoietic cell generation. Furthermore, in hematopoietic progenitor and stem-like cells, cAMP induction mitigated oxidative stress, created a redox-state balance, and enhanced C-X-C chemokine receptor type 4 (CXCR4) expression, benefiting the maintenance of these primitive cells. Collectively, our study provides insights and mechanistic details on the previously unrecognized role of cAMP signaling in regulating human hematopoietic development. These findings advance the mechanistic understanding of hematopoietic development toward the development of transplantable human hematopoietic cells for therapeutic needs.

Indexed as

Cell DifferentiationCyclic AMPEndotheliumGene Expression Regulation, DevelopmentalGuanine Nucleotide Exchange FactorsHematopoietic Stem CellsHumansOxidative StressPluripotent Stem CellsReceptors, CXCR4Signal TransductionCXCR4 protein, humanCyclic AMPGuanine Nucleotide Exchange FactorsRAPGEF3 protein, humanReceptors, CXCR4

Identifiers

PMID27117782
PMCPMC4939749

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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.