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)
  • Fasting for stem cell rejuvenation.
    González-Estévez C, Flores I
    Aging (Albany NY) 2020, 12(5), 4048—4049
  • DNA methyltransferase 1 (DNMT1) function is implicated in the age-related loss of cortical interneurons
    Hahn A, Bayer C, Pensold D, Tittelmeier J, Marx-Blümel L, González-Bermúdez L, Linde J, Groß J, Salinas-Riester G, Lingner T, von Maltzahn J, Spehr M, Pieler T, Urbach A, Zimmer-Bensch G
    bioRxiv 2020, https://doi.org/10.1101/2020.03.
  • 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
  • Correction: The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML.
    Kahl M, Brioli A, Bens M, Perner F, Kresinsky A, Schnetzke U, Hinze A, Sbirkov Y, Stengel S, Simonetti G, Martinelli G, Petrie K, Zelent A, Böhmer FD, Groth M, Ernst T, Heidel FH, Scholl S, Hochhaus A, Schenk T
    Leukemia 2020 (epub ahead of print)
  • Cohesin controls intestinal stem cell identity by maintaining association of Escargot with target promoters.
    Khaminets A, Ronnen-Oron T, Baldauf M, Meier E, Jasper H
    Elife 2020, 9, e48160
  • 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, 39(7), 1445-65 * 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)
  • Wnt7a Counteracts Cancer Cachexia.
    Schmidt M, Poser C, von Maltzahn J
    Mol Ther Oncolytics 2020, 16, 134-46