The Department of Biomedicine

BBB seminar: Karl Lenhard Rudolph

Epigenetic mechanisms of stem cell aging

Karl Lenhard Rudolph
Research Group on Stem Cell Aging, Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), Jena, Germany

Adult tissue stem cells contribute to the lifelong maintenance of organ homeostasis and regeneration. During aging, the functionality of stem cells declines and mutant stem cells gain clonal dominance, especially when mutations affect epigenome regulators. Our recent work revealed that alterations in epigenetic stress responses lead to an aberrant activation of developmental pathways that impair the self-renewal and regenerative capacity of muscle stem cells. The data indicate that alteration in epigenetic memory and stress responses contribute to the decline of stem cell function and possibly to the selection of stem cell mutation during aging. I will present current studies in the lab focusing on the identification of physiological and disease conditions as well as on molecular mechanisms that contribute to alterations of the epigenome in aging stem cells and how these processes lead to disease development in aging.

Selected publications:

Chen Z, Amro EM, Becker F, Hölzer M, Rasa SMM, Njeru SN, Han B, DiSanzo S, Chen Y, Tang D, Tao S, Hänold R, Groth M, Romanov VS, Kirkpatrick JM, Kraus JM, Kestler HA, Marz M, Ori A, Neri F, Morita Y, Rudolph KL. Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation. J Exp Med. 2018; in press

Ermolaeva M, Ori A, Neri F, Rudolph KL. Epigenetic integration of causal factors drives stem cell ageing. Nat Rev Mol Cell Biol. 2018; 25:778-86

Schwörer S, Becker F, Feller C, Baig AH, Köber U, Henze H, Kraus JM, Xin B, Lechel A, Lipka DB, Varghese CS, Schmidt M, Rohs R, Aebersold R, Medina KL, Kestler HA, Neri F, von Maltzahn J, Tümpel S, Rudolph KL. Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals. Nature. 2016; 540:428-32

Tang D, Tao S, Chen Z, Koliesnik IO, Gebert N, Calmes PG, Hörr V, Löffler B, Morita Y, Rudolph KL. Long-term dietary restriction improves repopulation but impairs lymphoid differentiation capacity of aging hematopoietic stem cells. J Exp Med. 2016; 213:535-53

Wang J, Sun Q, Morita Y, Jiang H, Groß A, Lechel A, Hildner K, Guachalla LM, Gompf A, Hartmann D, Schambach A, Wüstefeld T, Schrezenmeier H, Hofmann WK, Nakauchi H, Ju Z, Kestler HA, Zender L, Rudolph KL. Batf defines a differentiation checkpoint limiting hematopoietic stem cell self-renewal in response to DNA damage. Cell. 2012; 148:1001-14

Chairperson: Mathias Ziegler, Department of Biomedicine