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Research focus of Subarea 1.

Subarea 1: Stem Cell Aging

The individual research groups within Subarea 1 investigate the causes and consequences of stem cell aging. The research work spans from basic model organisms over genetic mouse models up to humanized mouse models engrafted with human stem cells.

According to the FLI, with the closure of two groups since 2016 the representation of invertebrate models of stem cell research was reduced in Subarea 1. The institute presumes that the recruitment of new groups should fill this gap.

The research is defined by four focus areas:

  • Cell-intrinsic mechanisms limiting the function of aging stem and progenitor cells,
  • Aging-associated alterations of stem cell niches and the systemic environment,
  • Mechanisms of clonal selection and epigenetic drifts in stem cell aging, and
  • Microbiota- and metabolism-induced impairments in stem cell function during aging (in context of the new focus area Microbiota and Aging currently being built up within Subarea 2).

Research focus of Subarea 1.

a) It is currently not well understood what mechanisms impair cellular functions in aging. b) The relative contribution of niche cells and systemic acting factors on stem cell aging have yet to be determined in different tissues. c) Clonal expansion of mutant cells associates with disease development in aging humans. Mechanistically, the process remains poorly understood. Changes in color intensity depict clonal dominance originating from stem (green) or progenitor cells (gray). d) Emerging evidences indicate that aging associated alterations in microbiota influence stem cell function and vice versa.

Publications

(since 2016)

2023

  • Human gene-engineered calreticulin mutant stem cells recapitulate MPN hallmarks and identify targetable vulnerabilities.
    Foßelteder J, Pabst G, Sconocchia T, Schlacher A, Auinger L, Kashofer K, Beham-Schmid C, Trajanoski S, Waskow C, Schöll W, Sill H, Zebisch A, Wölfler A, Thomas D, Reinisch A
    Leukemia 2023, 37(4), 843-53
  • Lentiviral in situ targeting of stem cells in unperturbed intestinal epithelium.
    Garside GB, Sandoval M, Beronja** S, Rudolph** KL
    BMC Biol 2023, 21(1), 6 ** co-corresponding authors
  • Molecular-defined clonal evolution in patients with classical myeloproliferative neoplasms.
    Hinze A, Rinke J, Crodel CC, Möbius S, Schäfer V, Heidel FH, Hochhaus A, Ernst T
    Br J Haematol 2023, 202(2), 308-17
  • A dysfunctional miR-1-TRPS1-MYOG axis drives ERMS by suppressing terminal myogenic differentiation.
    Hüttner SS, Henze H, Elster D, Koch P, Anderer U, von Eyss B, von Maltzahn J
    Mol Ther 2023, 31(9), 2612-32
  • Author Correction: IFNγ-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration.
    Omrani* O, Krepelova* A, Rasa SMM, Sirvinskas D, Lu J, Annunziata F, Garside G, Bajwa S, Reinhardt S, Adam L, Käppel S, Ducano N, Donna D, Ori A, Oliviero S, Rudolph KL, Neri F
    Nat Commun 2023, 14(1), 6302 * equal contribution
  • IFNγ-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration.
    Omrani* O, Krepelova* A, Rasa SMM, Sirvinskas D, Lu J, Annunziata F, Garside G, Bajwa S, Reinhardt S, Adam L, Käppel S, Ducano N, Donna D, Ori A, Oliviero S, Rudolph KL, Neri F
    Nat Commun 2023, 14(1), 6109 * equal contribution
  • T Cells Expressing a Modified FcγRI Exert Antibody-Dependent Cytotoxicity and Overcome the Limitations of CAR T-cell Therapy against Solid Tumors.
    Rasoulouniriana D, Santana-Magal N, Gutwillig A, Farhat-Younis L, Tal L, Amar S, Milyavsky M, Muddineni SSNA, Solomon N, Shpilt H, Dotan S, Pilpel N, Waskow C, Feinmesser M, Rider P, Carmi Y
    CANCER IMMUNOL RES 2023, 11(6), 792
  • Gene regulatory network inference with popInfer reveals dynamic regulation of hematopoietic stem cell quiescence upon diet restriction and aging.
    Rommelfanger* MK, Behrends* M, Chen Y, Martinez J, Bens M, Xiong L, Rudolph** KL, MacLean** AL
    bioRxiv 2023, 10.1101/2023.04.18.537360 * equal contribution, ** co-corresponding authors
  • Dynamic DNA methylation reveals novel cis-regulatory elements in mouse hematopoiesis.
    Schönung M, Hartmann M, Krämer S, Stäble S, Hakobyan M, Kleinert E, Aurich T, Cobanoglu D, Heidel FH, Fröhling S, Milsom MD, Schlesner M, Lutsik P, Lipka DB
    Exp Hematol 2023, 117, 24-42.e7
  • Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia.
    Straube* J, Eifert* T, Vu T, Janardhanan Y, Haldar R, von Eyss B, Cooper L, Bruedigam C, Ling VY, Cooper E, Patch AM, Bullinger L, Schnoeder TM, Bywater M, Heidel* FH, Lane* SW
    Leukemia 2023, 37(4), 741 * equal contribution