Evidence map›Paper›PMID 25870199›Full record

ArticleThe Journal of experimental medicine2015

Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis.

Miguel F Diaz, Nan Li, Hyun Jung Lee, Luigi Adamo, Siobahn M Evans, Hannah E Willey, Natasha Arora, Yu-Suke Torisawa, Dwayne A Vickers, Samantha A Morris and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Pooled it
  2. Therapeutic effects of alprostadil on CClMolecular and cellular biochemistry · 2026
    Article
  3. Article
  4. Mechanometabolism instructs hematopoietic stem cell specification.The Journal of experimental medicine · 2026
    Article
  5. Blood Flow Regulates Metabolism in Hematopoietic Development.Advances in experimental medicine and biology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Hematopoietic Stem Cells and the Immune System in Development and Aging.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 11 institutions in 3 countries.

Miguel F DiazProgram in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030.
Nan LiProgram in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030.
Hyun Jung LeeProgram in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030.
Luigi AdamoCenter for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
Siobahn M EvansProgram in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030.
Hannah E WilleyDepartment of Bioengineering, Rice University, Houston, TX 77030.
Natasha AroraStem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Harvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Yu-Suke TorisawaHarvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 Wyss Institute for Biologically Inspired Engineering at Harvard University and Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115 Wyss Institute for Biologically Inspired Engineering at Harvard University and Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115.
Dwayne A VickersBarnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA 02115.
Samantha A MorrisStem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Harvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Olaia NaveirasStem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Harvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Shashi K MurthyBarnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA 02115.
Donald E IngberHarvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 Wyss Institute for Biologically Inspired Engineering at Harvard University and Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115 Wyss Institute for Biologically Inspired Engineering at Harvard University and Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115.
George Q DaleyStem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Harvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 guillermo_garcia-cardena@hms.harvard.edu george.daley@childrens.harvard.edu pamela.l.wenzel@uth.tmc.edu.
Guillermo García-CardeñaCenter for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 Harvard Stem Cell Institute and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 guillermo_garcia-cardena@hms.harvard.edu george.daley@childrens.harvard.edu pamela.l.wenzel@uth.tmc.edu.
Pamela L WenzelProgram in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 Program in Children's Regenerative Medicine, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, and Immunology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 guillermo_garcia-cardena@hms.harvard.edu george.daley@childrens.harvard.edu pamela.l.wenzel@uth.tmc.edu.
Regenerative Medicine Institute · MXDana-Farber Cancer Institute · USHarvard University · USNortheastern University · USBrigham and Women's Hospital · USBrown Foundation · USHarvard Stem Cell Institute · USHoward Hughes Medical Institute · USInspire · CHRice University · USThe University of Texas Health Science Center at Houston · US

Funding

Customized stem cells for clinical application in blood disordersR24DK092760 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2011 to 2018
$10.7M
Identification of biomechanical pathways that promote hematopoiesisK01DK092365 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI WENZEL, PAMELA LYNN · 2011 to 2015
$708k
Howard Hughes Medical InstituteNIDDK NIH HHS K01 DK092365NIDDK NIH HHS R24 DK092760
6 · The paper itself

Abstract

Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in the developing embryo, yet the signals generated by hemodynamic forces that influence hematopoietic potential remain poorly defined. Here we show that fluid shear stress endows long-term multilineage engraftment potential upon early hematopoietic tissues at embryonic day 9.5, an embryonic stage not previously described to harbor HSCs. Effects on hematopoiesis are mediated in part by a cascade downstream of wall shear stress that involves calcium efflux and stimulation of the prostaglandin E2 (PGE2)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling axis. Blockade of the PGE2-cAMP-PKA pathway in the aorta-gonad-mesonephros (AGM) abolished enhancement in hematopoietic activity. Furthermore, Ncx1 heartbeat mutants, as well as static cultures of AGM, exhibit lower levels of expression of prostaglandin synthases and reduced phosphorylation of the cAMP response element-binding protein (CREB). Similar to flow-exposed cultures, transient treatment of AGM with the synthetic analogue 16,16-dimethyl-PGE2 stimulates more robust engraftment of adult recipients and greater lymphoid reconstitution. These data provide one mechanism by which biomechanical forces induced by blood flow modulate hematopoietic potential.

Indexed as

AnimalsBlood Flow VelocityCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinDinoprostoneEmbryo, MammalianMesonephrosMiceMice, KnockoutSignal TransductionStress, PhysiologicalCreb1 protein, mouseCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinDinoprostone

Identifiers

PMID25870199
PMCPMC4419354
OpenAlexW2127779718

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.