Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development in mice
Bowen Yan, Qingchen Yuan, Marco M. Buttigieg, Prabhjot Kaur, Annalisse R. McKee, Daniil E. Shabashvili, Caitlyn Vlasschaert, Alexander G. Bick, Michael J. Rauh, Olga A. Guryanova
Bowen Yan, Qingchen Yuan, Marco M. Buttigieg, Prabhjot Kaur, Annalisse R. McKee, Daniil E. Shabashvili, Caitlyn Vlasschaert, Alexander G. Bick, Michael J. Rauh, Olga A. Guryanova
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Research Letter Hematology Inflammation Metabolism

Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development in mice

Abstract

Authors

Bowen Yan, Qingchen Yuan, Marco M. Buttigieg, Prabhjot Kaur, Annalisse R. McKee, Daniil E. Shabashvili, Caitlyn Vlasschaert, Alexander G. Bick, Michael J. Rauh, Olga A. Guryanova

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Figure 1

Experimental Dnmt3a CH promotes obesity, impaired glucose metabolism, inflammation, and severe steatohepatitis.

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Experimental Dnmt3a CH promotes obesity, impaired glucose metabolism, in...
(A) CH and incident obesity risk; Cox proportional hazard regression. (B) Experimental workflow. (C) Body weight gain; mixed-effects analysis vs. Dnmt3a+/+ control; n = 7–8. (D) Food intake, averaged per cage. (E) Adipocyte size (SuperPlot, n = 3/group, 2 fields/animal); unpaired 2-tailed t test. (F–H) Plasma leptin (F), fasting glucose (G), and insulin (H) levels on HFD, plotted as quartiles. (I) Blood glucose levels after glucose load in fasted animals; mean ± SEM; 2-tailed Student’s t test vs. Dnmt3a+/+ controls. (J) Inflammatory monocytes in donor (CD45.2) or wild-type competitor/host (CD45.1) myeloid cells in spleen; paired 2-tailed Student’s t test. (K) Plasma MIP-1α and CXCL1; unpaired 2-tailed t test. (L) Liver histopathology (H&E; black arrow, acidophilic body; white arrows, ballooned hepatocytes; yellow arrows, inflammatory infiltrates; scale bar: 50 μm). (M) Steatohepatitis severity score (n = 3/group, 5 fields/animal). (N) Liver fibrosis (Masson’s trichrome staining) and percentage of positive area; unpaired 2-tailed t test with Welch’s correction (SuperPlot, n = 3/group, 4 fields/animal).