Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction.

JCI Insight
Ying WangKenneth Walsh

Abstract

Clonal hematopoiesis of indeterminate potential is prevalent in elderly individuals and associated with increased risks of all-cause mortality and cardiovascular disease. However, mouse models to study the dynamics of clonal hematopoiesis and its consequences on the cardiovascular system under homeostatic conditions are lacking. We developed a model of clonal hematopoiesis using adoptive transfer of unfractionated ten-eleven translocation 2-mutant (Tet2-mutant) bone marrow cells into nonirradiated mice. Consistent with age-related clonal hematopoiesis observed in humans, these mice displayed a progressive expansion of Tet2-deficient cells in multiple hematopoietic stem and progenitor cell fractions and blood cell lineages. The expansion of the Tet2-mutant fraction was also observed in bone marrow-derived CCR2+ myeloid cell populations within the heart, but there was a negligible impact on the yolk sac-derived CCR2- cardiac-resident macrophage population. Transcriptome profiling revealed an enhanced inflammatory signature in the donor-derived macrophages isolated from the heart. Mice receiving Tet2-deficient bone marrow cells spontaneously developed age-related cardiac dysfunction characterized by greater hypertrophy and fibrosi...Continue Reading

References

Aug 3, 2005·The Journal of Clinical Investigation·Ichiro ShiojimaKenneth Walsh
Dec 2, 2008·Cell Stem Cell·Elisa LaurentiAndreas Trumpp
Jan 11, 2012·Antioxidants & Redox Signaling·Dao-Fu DaiPeter S Rabinovitch
May 17, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Claudio Franceschi, Judith Campisi
Sep 24, 2014·The Journal of Experimental Medicine·Kaaweh MolawiMichael H Sieweke
Oct 9, 2014·Nature·Jianlong SunFernando D Camargo
Nov 27, 2014·The New England Journal of Medicine·Siddhartha JaiswalBenjamin L Ebert
Nov 27, 2014·The New England Journal of Medicine·Giulio GenoveseSteven A McCarroll
Apr 5, 2016·Nature Biotechnology·Nicolas L BrayLior Pachter
May 29, 2016·EMBO Molecular Medicine·Sonomi MaruyamaKenneth Walsh
Jun 22, 2017·The New England Journal of Medicine·Siddhartha JaiswalBenjamin L Ebert
Nov 17, 2017·Blood·Liran I Shlush
Jan 13, 2018·Nature·Alejo E Rodriguez-FraticelliFernando D Camargo
Feb 24, 2018·Journal of the American College of Cardiology·Soichi SanoKenneth Walsh
Sep 4, 2018·Cell·Sebastiaan De SchepperGuy Boeckxstaens
Sep 7, 2018·Circulation Journal : Official Journal of the Japanese Circulation Society·Soichi SanoKenneth Walsh
Jan 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rong LuIrving L Weissman
May 23, 2019·Nucleic Acids Research·Yuxing LiaoBing Zhang
Jul 12, 2019·Nature·Judith CampisiEric Verdin
Aug 21, 2019·Current Biology : CB·Neil A RobertsonTamir Chandra

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Citations

Jun 10, 2020·International Journal of Immunogenetics·Velizar Shivarov, Milena Ivanova
Aug 5, 2020·Journal of Clinical Medicine·Veronica PapaFrancesco Vieceli Dalla Sega
Nov 27, 2020·Cell Reports·Nuria Mencia-TrinchantChristopher E Mason
Feb 13, 2021·Life Sciences·Xuping LiYuanyuan Cheng
Oct 30, 2020·International Journal of Molecular Sciences·Oleg Kandarakov, Alexander Belyavsky
Feb 2, 2021·Frontiers in Cell and Developmental Biology·Nikolas James TsiouplisAgeliki Tsagaratou
Apr 10, 2021·Journal of the American College of Cardiology·Domingo A Pascual-FigalJosé J Fuster
Apr 10, 2021·Journal of the American College of Cardiology·Michael J Rauh
Apr 24, 2021·Trends in Cardiovascular Medicine·Nicholas W ChavkinKenneth Walsh
May 15, 2021·Nature Reviews. Genetics·Alexander J SilverMichael R Savona
May 11, 2021·Journal of Molecular and Cellular Cardiology·Cibele Rocha-ResendeLuigi Adamo
May 28, 2021·The New England Journal of Medicine·Satu Mustjoki, Neal S Young
Jun 16, 2021·The Journal of Experimental Medicine·Francisco CaiadoMarkus G Manz
Jul 3, 2021·Journal of the American College of Cardiology·Bing YuUNKNOWN National Heart, Lung, and Blood Institute TOPMed Consortium
Jul 3, 2021·Journal of the American College of Cardiology·José J Fuster
Jun 25, 2021·Cardiovascular Research·Ying WangKenneth Walsh
Aug 16, 2021·Current Problems in Cardiology·Chiara Mozzini, Mauro Pagani
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shadab FaramarziSeverina Pacifico
Aug 27, 2021·Circulation Journal : Official Journal of the Japanese Circulation Society·María A Zuriaga, José J Fuster

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Datasets Mentioned

BETA
GSE146812

Methods Mentioned

BETA
RNA-Seq
FACS
PCR
ELISA

Software Mentioned

GraphPad Prism
Vevo Lab
GENEWIZ
ImageJ
Fluidigm gene expression
Kallisto
GraphPad
RStudio
WebGestalt
Ensembl

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