Epigenetic regulation of DNA damage response in human hematopoietic stem cells

Epigenetic regulation of DNA damage response in human hematopoietic stem and progenitor cells of aged mice and humans

Principal Investigator: Claudia Waskow

The department Immunology of AgingExternal link headed by Claudia Waskow is located at the Leibniz Institute on AgingExternal link and explores age-related alterations in hematopoiesis and immune cell biology in mice and humans. Our aim is to improve life quality of humanity for extended periods of time in the future.

The outstanding relevance of immune senescence during aging along with the increased incidence and mortality rate through the progression of clonal hematopoiesis to blood cancer in elderly patients places hematopoiesis into the focus of age research. We generate and use innovative mouse models to explore the function of hematopoietic stem/progenitor cells (HSPCs) and immune cells from mice and humans, and we could show that the aging process of human HSPCs after transfer into mice occurs at the same rate compared to the aging process in situ. Thus, our innovative mouse models allow for in vivo analysis of consequences of experimental interventions on immune senescence. We further focus on consequences of epigenetic histone modification (methylation of lysine 4 in histone H3) on blood formation and could identify the key regulator for the expression of components of virtually all DNA repair pathways in hematopoietic stem and progenitor cells. We will now investigate the role of H3K4 methylation during aging of murine and human hematopoiesis using CRISPR/Cas9-mediated genome editing combined with in vivo and in vitro assay systems. We aim at the reduction of immune senescence based on an increased protection of hematopoietic stem and progenitor cells from replication-mediated functional impairments.

Doctoral researcher: Antea Jorgo

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