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)

2020

  • 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 (epub ahead of print)
  • Local and transient inhibition of p21 expression ameliorates age-related delayed wound healing.
    Jiang D, de Vries JC, Muschhammer J, Schatz S, Ye H, Hein T, Fidan M, Romanov VS, Rinkevich Y, Scharffetter-Kochanek K
    Wound Repair Regen 2020, 28(1), 49-60
  • Aneuploidy-inducing gene knockdowns overlap with cancer mutations and identify Orp3 as a B-cell lymphoma suppressor.
    Njeru* SN, Kraus* J, Meena* JK, Lechel A, Katz SF, Kumar M, Knippschild U, Azoitei A, Wezel F, Bolenz C, Leithäuser F, Gollowitzer A, Omrani O, Hoischen C, Koeberle A, Kestler** HA, Günes** C, Rudolph** KL
    Oncogene 2020 (epub ahead of print) * equal contribution, ** co-corresponding authors
  • SHP1 regulates a STAT6-ITGB3 axis in FLT3ITD-positive AML cells.
    Reich D, Kresinsky A, Müller JP, Bauer R, Kallenbach J, Schnoeder TM, Heidel FH, Fässler R, Mann M, Böhmer FD, Jayavelu AK
    Leukemia 2020 (epub ahead of print)
  • Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells.
    Scheffold A, Baig AH, Chen Z, von Löhneysen SE, Becker F, Morita Y, Avila AI, Groth M, Lechel A, Schmid F, Kraus JM, Kestler HA, Stilgenbauer S, Philipp M, Burkhalter MD
    Leukemia 2020 (epub ahead of print)
  • High Canonical Wnt/β-Catenin Activity Sensitizes Murine Hematopoietic Stem and Progenitor Cells to DNA Damage.
    Wang Y, Cui H, Tao S, Zeng T, Wu J, Tao Z, Zhang L, Zou B, Chen Z, Garside GB, Tang D
    Stem Cell Rev Rep 2020 (epub ahead of print)

2019

  • Analyzing Satellite Cell Function During Skeletal Muscle Regeneration by Cardiotoxin Injury and Injection of Self-delivering siRNA In Vivo.
    Ahrens* HE, Henze* H, Schüler SC, Schmidt M, Hüttner SS, von Maltzahn J
    J Vis Exp 2019 * equal contribution
  • Adaptive immunodeficiency accelerates the development of intestinal atrophy in telomere dysfunctional mice during ageing
    Bajwa S
    Dissertation 2019, Jena, Germany
  • Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation.
    Chen Z, Amro EM, Becker F, Hölzer M, Rasa SMM, Njeru SN, Han B, Di Sanzo S, Chen Y, Tang D, Tao S, Haenold R, Groth M, Romanov VS, Kirkpatrick JM, Kraus JM, Kestler HA, Marz M, Ori A, Neri F, Morita** Y, Rudolph** KL
    J Exp Med 2019, 216(1), 152-75 ** co-corresponding authors
  • Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation.
    Cocciardi S, Dolnik A, Kapp-Schwoerer S, Rücker FG, Lux S, Blätte TJ, Skambraks S, Krönke J, Heidel FH, Schnöder TM, Corbacioglu A, Gaidzik VI, Paschka P, Teleanu V, Göhring G, Thol F, Heuser M, Ganser A, Weber D, Sträng E, Kestler HA, Döhner H, Bullinger L, Döhner K
    Nat Commun 2019, 10(1), 2031