Frank Edenhofer
Group Leader at the University of Innsbruck
The Edenhofer lab
Subproject 10: Human-specific modulators of neural stem cell identity
This project aims to address unanswered questions regarding neural rejuvenation and cellular aging. Key objectives include identifying reprogramming barriers and targets for rejuvenation, deciphering metabolic dysfunction in aged neural stem cells (NSCs), and assessing CNS aging programs through modeling in 2D and 3D human cortical organoids. The proposal outlines specific tasks such as multi-omics trajectory analysis, lineage tree reconstruction, interspecies comparative analyses, and validation of candidate factors. Additionally, it emphasizes the importance of understanding the underlying molecular mechanisms driving cellular decline and dysfunction to guide the development of targeted interventions for successful regenerative therapies. The proposal highlights the use of novel models and experimental paradigms to further advance scientific understanding in the field.
Recent Publications
Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids
Barmpa K, Saraiva C, Lopez-Pigozzi D, Gomez-Giro G, Gabassi E, Spitz S, Brandauer K, Rodriguez Gatica JE, Antony P, Robertson G, Sabahi-Kaviani R, Bellapianta A, Papastefanaki F, Luttge R, Kubitscheck U, Salti A, Ertl P, Bortolozzi M, Matsas R, Edenhofer F, Schwamborn JC. Commun Biol. 2024 Nov 23;7(1):1561. doi: 10. 1038/s42003-024-07273-4. PMID: 39580573; PMCID: PMC11585662.
Increased cholesterol synthesis drives neurotoxicity in patient stem cell-derived model of multiple sclerosis
Ionescu RB, Nicaise AM, Reisz JA, Williams EC, Prasad P, Willis CM, Simões- Abade MBC, Sbarro L, Dzieciatkowska M, Stephenson D, Suarez Cubero M, Rizzi S, Pirvan L, Peruzzotti-Jametti L, Fossati V, Edenhofer F, Leonardi T, Frezza C, Mohorianu I, D’Alessandro A, Pluchino S. Cell Stem Cell. 2024 Nov 7;31(11):1574-1590. e11. doi: 10. 1016/j. stem. 2024. 09. 014. Epub 2024 Oct 21. PMID: 39437792.
Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes
Heimdörfer D, Vorleuter A, Eschlböck A, Spathopoulou A, Suarez-Cubero M, Farhan H, Reiterer V, Spanjaard M, Schaaf CP, Huber LA, Kremser L, Sarg B, Edenhofer F, Geley S, de Araujo MEG, Huettenhofer A. Am J Hum Genet. 2024 Jul 11;111(7):1383-1404. doi: 10. 1016/j. ajhg. 2024. 05. 023. Epub 2024 Jun 21. PMID: 38908375; PMCID: PMC11267527.
Integrative metabolomics-genomics analysis identifies key networks in a stem cell-based model of schizophrenia
Spathopoulou A, Sauerwein GA, Marteau V, Podlesnic M, Lindlbauer T, Kipura T, Hotze M, Gabassi E, Kruszewski K, Koskuvi M, Réthelyi JM, Apáti Á, Conti L, Ku M, Koal T, Müller U, Talmazan RA, Ojansuu I, Vaurio O, Lähteenvuo M, Lehtonen Š, Mertens J, Kwiatkowski M, Günther K, Tiihonen J, Koistinaho J, Trajanoski Z, Edenhofer F. Mol Psychiatry. 2024 Oct;29(10):3128-3140. doi: 10. 1038/s41380-024-02568-8. Epub 2024 Apr 29. PMID: 38684795; PMCID: PMC11449784.
Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model and pilot data
Klein T, Grüner J, Breyer M, Schlegel J, Schottmann NM, Hofmann L, Gauss K, Mease R, Erbacher C, Finke L, Klein A, Klug K, Karl-Schöller F, Vignolo B, Reinhard S, Schneider T, Günther K, Fink J, Dudek J, Maack C, Klopocki E, Seibel J, Edenhofer F, Wischmeyer E, Sauer M, Üçeyler N. Brain Commun. 2024 Apr 3;6(2):fcae095. doi: 10. 1093/braincomms/fcae095. PMID: 38638148; PMCID: PMC11024803.
Single-cell Profiling of Reprogrammed Human Neural Stem Cells Unveils High Similarity to Neural Progenitors in the Developing Central Nervous System
Spathopoulou A, Podlesnic M, De Gaetano L, Kirsch EM, Tisch M, Finotello F, Aigner L, Günther K, Edenhofer F. Stem Cell Rev Rep. 2024 Jul;20(5):1325-1339. doi: 10. 1007/s12015-024-10698-3. Epub 2024 Mar 22. PMID: 38519702; PMCID: PMC11222274.
Generation of the human induced pluripotent stem cell line (IBKMOLi003-A) from PBMCs of a vascular Ehlers-Danlos syndrome (vEDS) patient carrying the heterozygous nonsense mutation c
Höpperger S, Spathopoulou A, Mayer-Suess L, Suarez-Cubero M, Sillaber K, Spreiz A, Kiechl S, Edenhofer F, Fellner L. 430C > T (p. Q105*) in the COL3A1 gene. Stem Cell Res. 2024 Mar;75:103321. doi: 10. 1016/j. scr. 2024. 103321. Epub 2024 Jan 26. PMID: 38301384.
The promise of genetic screens in human in vitro brain models
Beirute-Herrera J, López-Amo Calvo B, Edenhofer F, Esk C. Biol Chem. 2023 Sep 12;405(1):13-24. doi: 10. 1515/hsz-2023-0174. PMID: 37697643.
Emerging Role of miR-21-5p in Neuron-Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease
Garcia G, Pinto S, Ferreira S, Lopes D, Serrador MJ, Fernandes A, Vaz AR, Mendonça A, Edenhofer F, Malm T, Koistinaho J, Brites D. Cells. 2022 Oct 26;11(21):3377. doi: 10. 3390/cells11213377. PMID: 36359774; PMCID: PMC9655962.
ADHD-associated PARK2 copy number variants: A pilot study on gene expression and effects of supplementary deprivation in patient-derived cell lines
Radtke F, Palladino VS, McNeill RV, Chiocchetti AG, Haslinger D, Leyh M, Gersic D, Frank M, Grünewald L, Klebe S, Brüstle O, Günther K, Edenhofer F, Kranz TM, Reif A, Kittel-Schneider S. Am J Med Genet B Neuropsychiatr Genet. 2022 Oct;189(7-8):257-270. doi: 10. 1002/ajmg. b. 32918. Epub 2022 Aug 16. PMID: 35971782.
Generation of the human induced pluripotent stem cell line (IBKMOLi002-A) from PBMCs of a patient carrying the heterozygous L271H mutation of the voltage-gated calcium channel subunit Cav1
Tisch M, Carmen De Mingo Alemany M, Suarez-Cubero M, Fauth C, Defrancesco M, Zschocke J, Günther K, Edenhofer F. 3-encoding CACNA1D gene. Stem Cell Res. 2022 May;61:102784. doi: 10. 1016/j. scr. 2022. 102784. Epub 2022 Apr 9. PMID: 35453044.