ArticleCell stem cell2022
Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.
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Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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172citing papers in PubMed
35.4field-weighted citation impact, top 1% of its field
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Who cites it
172 citing papers in PubMed, 243 citations in OpenAlex.
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112 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors at 9 institutions in 4 countries.
Ruzhica BogeskaDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany.
Ana-Matea MikecinDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany.
Paul KaschutnigDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany.
Malak FawazDepartment of Medicine, Hematology/Oncology, Goethe University Hospital Frankfurt, 60590 Frankfurt, Germany.
Marleen Büchler-SchäffDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany.
Duy LeProgram in Immunology, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Miguel GanuzaDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London London EC1M 6BQ, UK.
Angelika VollmerInstitute of Molecular Medicine, Stem Cells and Aging, Aging Research Center, Ulm University, 89081 Ulm, Germany.
Stella V PaffenholzDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany.
Noboru AsadaRuth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Esther Rodriguez-CorreaDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany.
Felix FrauhammerFaculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany; Division of Applied Bioinformatics, DKFZ, 69120 Heidelberg, Germany.
Florian BuettnerDepartment of Medicine, Hematology/Oncology, Goethe University Hospital Frankfurt, 60590 Frankfurt, Germany; The German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Frankfurt Cancer Institute, 60590 Frankfurt, Germany.
Melanie BallDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany.
Julia KnochDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany.
Sina StäbleDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, DKFZ, 69120 Heidelberg, Germany.
Dagmar WalterDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany.
Amelie PetriDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany.
Martha J Carreño-GonzalezDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany.
Vinona WagnerDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany.
Benedikt BrorsDivision of Applied Bioinformatics, DKFZ, 69120 Heidelberg, Germany.
Simon HaasHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; The German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, DKFZ, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, Heidelberg, Germany; Berlin Institute of Health (BIH), Charité Universitätsmedizin, 10178 Berlin, Germany; Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
Daniel B LipkaThe German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, DKFZ, 69120 Heidelberg, Germany; National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany; Faculty of Medicine, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Marieke A G EssersHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, Heidelberg, Germany; Division of Inflammatory Stress in Stem Cells, DKFZ, 69120 Heidelberg, Germany.
Vivienn WeruDivision of Biostatistics, DKFZ, 69120 Heidelberg, Germany.
Tim Holland-LetzDivision of Biostatistics, DKFZ, 69120 Heidelberg, Germany.
Jan-Philipp MallmDivision of Chromatin Networks, DKFZ, 69120 Heidelberg, Germany.
Karsten RippeDivision of Chromatin Networks, DKFZ, 69120 Heidelberg, Germany.
Stephan KrämerFaculty of Biosciences, University of Heidelberg, 69120 Heidelberg, Germany; Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, DKFZ, 69120 Heidelberg, Germany; Biomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, 86159 Augsburg, Germany; Bioinformatics and Omics Data Analysis, DKFZ, 69120 Heidelberg, Germany.
Matthias SchlesnerBiomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, 86159 Augsburg, Germany; Bioinformatics and Omics Data Analysis, DKFZ, 69120 Heidelberg, Germany.
Shannon McKinney FreemanDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Maria Carolina FlorianStem Cell Aging Group, Regenerative Medicine Program, The Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Katherine Y KingProgram in Immunology, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Division of Infectious Diseases, Baylor College of Medicine, Houston, TX 77030, USA.
Paul S FrenetteRuth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Michael A RiegerDepartment of Medicine, Hematology/Oncology, Goethe University Hospital Frankfurt, 60590 Frankfurt, Germany; The German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Frankfurt Cancer Institute, 60590 Frankfurt, Germany; Cardio-Pulmonary Institute, 60590 Frankfurt, Germany.
Michael D MilsomDivision of Experimental Hematology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, Heidelberg, Germany. Electronic address: michael.milsom@dkfz.de.
German Cancer Research Center · DEHeidelberg University · DEGoethe University Frankfurt · DEAlbert Einstein College of Medicine · USBaylor College of Medicine · USSt. Jude Children's Research Hospital · USUniversity of Augsburg · DEInstitut d'Investigació Biomédica de Bellvitge · ESUniversität Ulm · DE
Funding
Regulation and function of hematopoietic stem cell nichesR01DK056638 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GRITSMAN, KIRA · 2000 to 2023
$8.7MImpact of Infection and Inflammation on Primitive HematopoiesisR35HL155672 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Katherine Yudeh King · 2021 to 2026
$5.1MMechanisms regulating the aging of HSC nichesR01DK112976 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI FRENETTE, PAUL S · 2018 to 2021
$1.5MThe mechanism of Batf2-mediated HSC differentiation during chronic infectionF31HL154661 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI LE, DUY TRI · 2020 to 2022
$103kNHLBI NIH HHS F31 HL154661NHLBI NIH HHS R35 HL155672NIDDK NIH HHS R01 DK056638NIDDK NIH HHS R01 DK112976
Abstract
Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functional HSCs following challenge with inflammation or bacterial infection, with no evidence of any recovery up to 1 year afterward. HSCs from challenged mice demonstrated multiple cellular and molecular features of accelerated aging and developed clinically relevant blood and bone marrow phenotypes not normally observed in aged laboratory mice but commonly seen in elderly humans. In vivo HSC self-renewal divisions were absent or extremely rare during both challenge and recovery periods. The progressive, irreversible attrition of HSC function demonstrates that temporally discrete inflammatory events elicit a cumulative inhibitory effect on HSCs. This work positions early/mid-life inflammation as a mediator of lifelong defects in tissue maintenance and regeneration.
Indexed as
HematopoiesisHematopoietic Stem CellsAgedAgingAnimalsBone MarrowHumansInflammationMiceaccelerated agingagingclonal hematopoiesishematopoietic stem cellsHSCsinflammaginginflammationself-renewalstem cell exhaustionstress hematopoiesis
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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 Socratic graph.