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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)

2021

  • Stimulation of Non-canonical NF-κB Through Lymphotoxin-β-Receptor Impairs Myogenic Differentiation and Regeneration of Skeletal Muscle.
    Schmidt M, Weidemann A, Poser C, Bigot A, von Maltzahn J
    Front Cell Dev Biol 2021, 9, 721543
  • Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality.
    Schüler SC, Kirkpatrick* JM, Schmidt* M, Santinha D, Koch P, Di Sanzo S, Cirri E, Hemberg M, Ori** A, von Maltzahn** J
    Cell Rep 2021, 35(10), 109223 * equal contribution, ** co-senior authors
  • Correction: Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging.
    Tang D, Tao S, Chen Z, Koliesnik IO, Calmes PG, Hoerr V, Han B, Gebert N, Zörnig M, Löffler B, Morita Y, Rudolph KL
    J Exp Med 2021, 218(1)
  • Immunoproteasome Function in Normal and Malignant Hematopoiesis.
    Tubío-Santamaría N, Ebstein F, Heidel FH, Krüger E
    Cells 2021, 10(7)
  • Chapter Nine - Regulation of muscle stem cell function
    von Maltzahn J
    In: Vitamins and Hormones, Hormones and Stem Cells (edited by Gerald Litwack) 2021, 16, 295-311, Elsevier, Amsterdam
  • Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration.
    Yi* W, Zhang* Y, Liu B, Zhou Y, Liao D, Qiao X, Gao D, Xie T, Yao Q, Zhang Y, Qiu Y, Huang G, Chen Z, Chen C, Ju Z
    Cell Rep 2021, 34(13), 108922 * equal contribution

2020

  • Decreased plasticity of aged hematopoietic stem and progenitor cells to adapt to nutrient availability
    Amro E
    Dissertation 2020, Jena, Germany
  • Distinct effects of ruxolitinib and interferon-alpha on murine JAK2V617F myeloproliferative neoplasm hematopoietic stem cell populations.
    Austin RJ, Straube J, Bruedigam C, Pali G, Jacquelin S, Vu T, Green J, Gräsel J, Lansink L, Cooper L, Lee SJ, Chen NT, Lee CW, Haque A, Heidel FH, D'Andrea R, Hill GR, Mullally A, Milsom MD, Bywater M, Lane SW
    Leukemia 2020, 34(4), 1075-89
  • Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 Expression.
    Brandt S, Ballhause TM, Bernhardt A, Becker A, Salaru D, Le-Deffge HM, Fehr A, Fu Y, Philipsen L, Djudjaj S, Müller AJ, Kramann R, Ibrahim M, Geffers R, Siebel C, Isermann B, Heidel FH, Lindquist JA, Mertens PR
    J Am Soc Nephrol 2020, 31(11), 2589-608
  • Impaired metabolic stress responses in hematopoietic stem cell aging
    Chen Y
    Dissertation 2020, Jena, Germany