ArticleCell reports2023
Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Single-Cell RNA-seq Analysis Reveals Distinct Tumor and Immunosuppressive T-Cell Phenotypes in Patients with CLL Treated with Ibrutinib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Gpr171 regulates embryonic hematopoietic stem cell emergence via ERK1/2 and Notch signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Stem Cell Niche Concept: Search for Current Expert Consensus.International journal of molecular sciences · 2025Review
- Article
- Influence of the Bone Marrow Microenvironment on Hematopoietic Stem Cell Behavior Post-Allogeneic Transplantation: Development of Clonal Hematopoiesis and Telomere Dynamics.International journal of molecular sciences · 2024Article
- CXCL8 and its cognate receptors CXCR1/CXCR2 in primary myelofibrosis.Haematologica · 2024Review
- Article
- Fishing Innate Immune System Properties through the Transcriptomic Single-Cell Data ofBiology · 2023Review
Corrections and comments
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Authors and funding
27 authors at 5 institutions in 2 countries.
Vera BinderDr. von Hauner Childrens' Hospital, University Hospital Ludwig Maximillian's University, Department of Pediatric Hematology/Oncology, 80337 Munich, Germany.
Wantong LiThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Muhammad FaisalThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Konur OymanThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Donn L CalkinsThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Jami ShafferThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Emily M TeetsThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Steven SherThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Andrew MagnotteThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Alex BelardoThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
William DeruelleThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
T Charles GregoryThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; The Ohio State University College of Medicine, Department of Biomedical Informatics, Columbus, OH 43210, USA.
Shelley OrwickThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Elliott J HagedornBoston University School of Medicine, Department of Medicine, Boston, MA 02118, USA.
Julie R PerlinStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA.
Serine AvagyanDana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA 02115, USA.
Asher LichtigStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA.
Francesca BarrettStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA.
Michelle AmmermanStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA.
Song YangStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA.
Yi ZhouStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA.
William E CarsonThe Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Heather R ShiveLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
James S BlachlyThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; The Ohio State University College of Medicine, Department of Biomedical Informatics, Columbus, OH 43210, USA.
Rosa LapalombellaThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
Leonard I ZonStem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA; Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA 02138, USA.
Bradley W BlaserThe Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA. Electronic address: bradley.blaser@osumc.edu.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USBoston Children's Hospital · USBoston University · USLudwig-Maximilians-Universität München · DENational Cancer Institute · US
Funding
TRANSCRIPTION FACTOR GATA-1 IN TERMINAL ERYTHROID DEVELOPMENTP01HL032262 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1985 to 2021
$38.9MTranscriptional and epigenetic heterogeneity of stem/progenitor cellsP01HL131477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI DANIEL G TENEN · 2017 to 2026
$24.6MUM1 Supplement for Early Therapeutic Trials with Phase 2 IntentUM1CA186712 · NCI · OHIO STATE UNIVERSITY · PI SUSANNE M ARNOLD, WILLIAM E. CARSON · 2014 to 2026
$19.3MPhysician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1MStem cells for therapeutics discovery in genetic blood disordersU01HL134812 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q, LIPTON, JEFFREY M · 2016 to 2022
$8.3MMolecular Circuits in the Hematopoietic Stem Cell NicheRC2DK120535 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2020 to 2024
$8.2MTranscriptional response to signaling during hematopoiesisR01HL144780 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI ZON, LEONARD IRA · 2019 to 2022
$2.1MEpigenetic control of vascular niche capacity to support hematopoiesis.R01DK128238 · NIDDK · OHIO STATE UNIVERSITY · PI BLASER, BRADLEY WAYNE · 2021 to 2025
$1.5MDeconstructing the Hematopoietic Stem Cell NicheK01DK111790 · NIDDK · BOSTON MEDICAL CENTER · PI HAGEDORN, ELLIOTT JENNINGS · 2017 to 2021
$792kRegulation of zebrafish hematopoiesis by the sinusoidal endothelial cell nicheK08DK111920 · NIDDK · OHIO STATE UNIVERSITY · PI BLASER, BRADLEY WAYNE · 2017 to 2021
$759kTargeting Autocrine Hepatocyte Growth Factor (HGF) Production as a Therapeutic Modality in Acute Myeloid Leukemia (AML)R21CA263337 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLASER, BRADLEY WAYNE, WANG, VICTORIA · 2023 to 2024
$415kNCI NIH HHS R21 CA263337NCI NIH HHS T32 CA009172NCI NIH HHS UM1 CA186712NHLBI NIH HHS P01 HL032262NHLBI NIH HHS P01 HL131477NHLBI NIH HHS R01 HL144780NHLBI NIH HHS U01 HL134812NIDDK NIH HHS K01 DK111790NIDDK NIH HHS K08 DK111920NIDDK NIH HHS R01 DK128238NIDDK NIH HHS RC2 DK120535
Abstract
Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling this are poorly understood. Genetically barcoded genome editing of synthetic target arrays for lineage tracing (GESTALT) zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-δ, encoded by prkcda) increases the number of HSC clones by up to 80% and expands polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augment HSC competition for residency within the niche and expand defined niche populations. CXCL8 induces association of PKC-δ with the focal adhesion complex, activating extracellular signal-regulated kinase (ERK) signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche that is controlled by CXCL8 and PKC and has significant impact on HSC phylogenetic and phenotypic fate.
Indexed as
Endothelial CellsZebrafishAnimalsHematopoiesisHematopoietic Stem CellsHumansInterleukin-8PhylogenyProtein Kinase C-deltaStem Cell NicheInterleukin-8Protein Kinase C-deltaCP: Stem cell researchhematopoiesis, CXCL8, PKC, barcoding, lineage tracing, zebrafish, vascular niche, hematopoietic niche, microenvironment, clonality
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