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 alter ations in microbiota influence stem cell function and vice versa.
Publications
(since 2016)
2018
- Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration.
Mayerl S, Schmidt M, Doycheva D, Darras VM, Hüttner SS, Boelen A, Visser TJ, Kaether C, Heuer** H, von Maltzahn** J
Stem Cell Reports 2018, 10(6), 1959-74 ** co-corresponding authors - The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function.
Mohr J, Dash BP, Schnoeder TM, Wolleschak D, Herzog C, Tubio Santamaria N, Weinert S, Godavarthy S, Zanetti C, Naumann M, Hartleben B, Huber TB, Krause DS, Kähne T, Bullinger L, Heidel FH
Leukemia 2018, 32(5), 1211-21 - Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice.
Müller* C, Zidek* LM, Ackermann T, de Jong T, Liu P, Kliche V, Zaini MA, Kortman G, Harkema L, Verbeek DS, Tuckermann JP, von Maltzahn J, de Bruin A, Guryev V, Wang ZQ, Calkhoven CF
Elife 2018, 7, e34985 * equal contribution - CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages.
Percin GI, Eitler J, Kranz A, Fu J, Pollard JW, Naumann R, Waskow C
Nat Commun 2018, 9(1), 5279 - Dysregulation of chemokine receptor expression and function in leukocytes from ALS patients.
Perner C, Perner F, Stubendorff B, Förster M, Witte OW, Heidel FH, Prell T, Grosskreutz J
J Neuroinflammation 2018, 15(1), 99 - Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms.
Prestipino A, Emhardt AJ, Aumann K, O'Sullivan D, Gorantla SP, Duquesne S, Melchinger W, Braun L, Vuckovic S, Boerries M, Busch H, Halbach S, Pennisi S, Poggio T, Apostolova P, Veratti P, Hettich M, Niedermann G, Bartholomä M, Shoumariyeh K, Jutzi JS, Wehrle J, Dierks C, Becker H, Schmitt-Graeff A, Follo M, Pfeifer D, Rohr J, Fuchs S, Ehl S, Hartl FA, Minguet S, Miething C, Heidel FH, Kröger N, Triviai I, Brummer T, Finke J, Illert AL, Ruggiero E, Bonini C, Duyster J, Pahl HL, Lane SW, Hill GR, Blazar BR, von Bubnoff N, Pearce EL, Zeiser R
SCI TRANSL MED 2018, 10(429) - Towards prevention of loss of muscle stem cell function during aging and prevention of cancer cachexia.
Schmidt M
Dissertation 2018, Jena, Germany - A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells.
Siegle* L, Schwab* JD, Kühlwein* SD, Lausser L, Tümpel S, Pfister AS, Kühl** M, Kestler** HA
PLoS One 2018, 13(3), e0195126 * equal contribution, ** co-senior authors - Senescence mirrors the extent of liver fibrosis in chronic hepatitis C virus infection.
Wandrer F, Han B, Liebig S, Schlue J, Manns MP, Schulze-Osthoff K, Bantel H
Aliment Pharmacol Ther 2018, 48(3), 270-80
