ArticleThe Journal of experimental medicine2015
Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence.
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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 41 papers.
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41 citing papers in PubMed, 54 citations in OpenAlex.
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Authors and funding
13 authors at 6 institutions in 1 country.
Peter Geon KimDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Haruko NakanoDepartment of Molecular Cell and Developmental Biology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095.
Partha P DasDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Michael J ChenDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
R Grant RoweDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Stephanie S ChouDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Samantha J RossDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Kathleen M SakamotoDivision of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Stanford University School of Medicine, Stanford, CA 94305.
Leonard I ZonDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Thorsten M SchlaegerDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Stuart H OrkinDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Atsushi NakanoDepartment of Molecular Cell and Developmental Biology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095.
George Q DaleyDivision of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; Howard Hughes Medical Institute, Harvard Stem Cell Institute; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 george.daley@childrens.harvard.edu.
Howard Hughes Medical Institute · USHarvard Stem Cell Institute · USBroad Center · USBoston Children's Hospital · USDana-Farber Cancer Institute · USLucile Packard Children's Hospital · 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
$10.7MHuman Pluripotent Stem Cell and Progenitor Models of Cardiac and Blood DiseasesU01HL100001 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q, ORKIN, STUART H · 2009 to 2015
$8.9MEMBRYONIC HEMATOPOIESISR01HL048801 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 1992 to 2016
$5.7MHoward Hughes Medical InstituteNHLBI NIH HHS R01 HL048801NHLBI NIH HHS U01 HL100001NHLBI NIH HHS UO1-HL100001NIDDK NIH HHS R24 DK092760NIDDK NIH HHS R24-DK092760
Abstract
Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta-gonad-mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)-cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA-CREB and BMP pathways in isolated AGM VE-cadherin(+) cells from mid-gestation embryos, we demonstrate that PKA-CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA-CREB-BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-to-hematopoietic transition.
Indexed as
AnimalsBone Morphogenetic ProteinsCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinEmbryo, MammalianEndothelial CellsHematopoietic Stem CellsMesonephrosMiceMice, Mutant StrainsSignal TransductionSodium-Calcium ExchangerBone Morphogenetic ProteinsCreb1 protein, mouseCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinNCX1 protein, mouseSodium-Calcium Exchanger
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