Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells.

Autor: Carrelha J; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. j.carrelha@imperial.ac.uk.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. j.carrelha@imperial.ac.uk.; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, UK. j.carrelha@imperial.ac.uk., Mazzi S; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Winroth A; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Hagemann-Jensen M; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Ziegenhain C; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.; Division of Medical Systems Bioengineering, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Högstrand K; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Seki M; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Brennan MS; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Lehander M; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Wu B; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Meng Y; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Markljung E; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Norfo R; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; Interdepartmental Centre for Stem Cells and Regenerative Medicine (CIDSTEM), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy., Ishida H; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Belander Strålin K; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden., Grasso F; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Simoglou Karali C; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Aliouat A; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Hillen A; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Chari E; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Siletti K; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.; Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands., Thongjuea S; Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Mead AJ; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; Cancer and Haematology Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Linnarsson S; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Nerlov C; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Sandberg R; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Yoshizato T; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Woll PS; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden., Jacobsen SEW; Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. sten.eirik.jacobsen@ki.se.; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. sten.eirik.jacobsen@ki.se.; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden. sten.eirik.jacobsen@ki.se.; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. sten.eirik.jacobsen@ki.se.; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden. sten.eirik.jacobsen@ki.se.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Jun; Vol. 25 (6), pp. 1007-1019. Date of Electronic Publication: 2024 May 30.
DOI: 10.1038/s41590-024-01845-6
Abstrakt: Rare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cells, established models of hematopoiesis implicate only one mandatory differentiation pathway for each blood cell lineage. Here, we establish a nonhierarchical relationship between distinct stem cells that replenish all blood cell lineages and stem cells that replenish almost exclusively platelets, a lineage essential for hemostasis and with important roles in both the innate and adaptive immune systems. These distinct stem cells use cellularly, molecularly and functionally separate pathways for the replenishment of molecularly distinct megakaryocyte-restricted progenitors: a slower steady-state multipotent pathway and a fast-track emergency-activated platelet-restricted pathway. These findings provide a framework for enhancing platelet replenishment in settings in which slow recovery of platelets remains a major clinical challenge.
(© 2024. The Author(s).)
Databáze: MEDLINE
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