Journal article
Persistent epigenetic signals propel a senescence-associated secretory phenotype and trained innate immunity in CD34 hematopoietic stem cells from diabetic patients
Maria Cristina Vinci, Sarah Costantino, Giulia Damiano, Erica Rurali, Raffaella Rinaldi, Vera Vigorelli, Annalisa Sforza, Ermes Carulli, Sergio Pirola, Giorgio Mastroiacovo, Angela Raucci, Assam El-Osta, Francesco Paneni, Giulio Pompilio
Cardiovascular Diabetology | BMC | Published : 2024
Abstract
BACKGROUND: Diabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed to investigate in humans whether epigenetic signals involved in immune cell activation and inflammation are initiated in hematopoietic stem/progenitor cells (HSPCs) and transferred to differentiated progeny. METHODS AND RESULTS: High glucose (HG)-exposure of cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by cell proliferation lowering, ROS production, telomere shortening, up-regulation of p21 and p27genes, upregulation of NFkB-p65 transcription factor and increased secretion of the inflammatory cytokin..
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Awarded by Ministero della Salute
Funding Acknowledgements
This research was funded by Ricerca Corrente of the Italian Ministry of Health and the Swiss National Science Foundation (n. 310030_197557, to F.P.).