Epigenetic Engineering
We investigate, what determines and protects the identity of the cell types in the body, particularly the brain.
We are concentrating on three important mechanisms in this context:
We investigate, what determines and protects the identity of the cell types in the body, particularly the brain.
We are concentrating on three important mechanisms in this context:
About our Research
Helmholtz Munich | Stricker LabThe operating principles of Master Transcription Factors
Master transcription factors (Master TFs) play a pivotal role in activating specific cellular programs while simultaneously repressing others. Certain Master TFs, often referred to as 'reprogramming factors,' possess the remarkable ability to transform fully differentiated cells into other cell types. Nevertheless, the mechanisms behind this transformation process remain incompletely understood.
To shed light on this intricate process, we employ both in vitro and in vivo reprogramming strategies, leverage CRISPR methodology, and harness the power of single-cell sequencing technology. Our research aims to uncover the factors that dictate cell identity and delve into the intricate workings of these factors (Hersbach et al., 2022 and ongoing/ unpublished)."
Helmholtz Munich | Stricker LabThe Functional Relevance of Chromatin Marks
Chromatin represents the macro-molecular structure formed by DNA, proteins, and RNA within eukaryotic cell nuclei. Variations in its content, topology, and chemical modifications are believed to underlie gene activity and epigenetic regulation. Nevertheless, the intricate nature of chromatin makes it challenging to pinpoint which specific chromatin features play a causal role in gene activity. To address this challenge, we employ cutting-edge epigenome editing technologies based on CRISPR approaches to directly assess the significance of particular chromatin marks. Using this approach, we recently demonstrated that DNA methylation on the promoter region of the Master-TF Soxl controls the rejuvenation potential of aged neural stem cells (Baumann et al., 2019).
Helmholtz Munich | Stricker LabThe Significance of the Noncoding and Repetitive Genome
The mammalian genome is vast, yet protein-coding genes are relatively scarce. Noncoding, repetitive, and structural transcripts are much more prevalent. Historically, these transcripts have been somewhat overlooked within the context of cell identity. However, recent unpublished data suggests that they may play a pivotal role in defining cell identity and plasticity. To investigate this potential, we employ innovative computational approaches to identify new candidates among these transcripts. Subsequently, we utilize CRISPR-based epigenome editing techniques to assess their functional relevance.
Helmholtz Munich | Stricker LabThe operating principles of Master Transcription Factors
Master transcription factors (Master TFs) play a pivotal role in activating specific cellular programs while simultaneously repressing others. Certain Master TFs, often referred to as 'reprogramming factors,' possess the remarkable ability to transform fully differentiated cells into other cell types. Nevertheless, the mechanisms behind this transformation process remain incompletely understood.
To shed light on this intricate process, we employ both in vitro and in vivo reprogramming strategies, leverage CRISPR methodology, and harness the power of single-cell sequencing technology. Our research aims to uncover the factors that dictate cell identity and delve into the intricate workings of these factors (Hersbach et al., 2022 and ongoing/ unpublished)."
Helmholtz Munich | Stricker LabThe Functional Relevance of Chromatin Marks
Chromatin represents the macro-molecular structure formed by DNA, proteins, and RNA within eukaryotic cell nuclei. Variations in its content, topology, and chemical modifications are believed to underlie gene activity and epigenetic regulation. Nevertheless, the intricate nature of chromatin makes it challenging to pinpoint which specific chromatin features play a causal role in gene activity. To address this challenge, we employ cutting-edge epigenome editing technologies based on CRISPR approaches to directly assess the significance of particular chromatin marks. Using this approach, we recently demonstrated that DNA methylation on the promoter region of the Master-TF Soxl controls the rejuvenation potential of aged neural stem cells (Baumann et al., 2019).
Helmholtz Munich | Stricker LabThe Significance of the Noncoding and Repetitive Genome
The mammalian genome is vast, yet protein-coding genes are relatively scarce. Noncoding, repetitive, and structural transcripts are much more prevalent. Historically, these transcripts have been somewhat overlooked within the context of cell identity. However, recent unpublished data suggests that they may play a pivotal role in defining cell identity and plasticity. To investigate this potential, we employ innovative computational approaches to identify new candidates among these transcripts. Subsequently, we utilize CRISPR-based epigenome editing techniques to assess their functional relevance.
Team Members
Publications
Stricker SH, Pereira CF. (2024) Reprogramming Stars #15: Colliding Cellular Reprogramming Paths, an Interview with Prof. Dr. Stefan Stricker. Cell Reprogram 26(2):37-42 10.1089/cell.2024.29115.shs
Windisch R, Soliman S, Hoffmann A, Chen-Wichmann L, Danese A, Vosberg S, Lutz S, Kellner C, Monte RE, Hartmann L, Schneider S, Beier F, Strobl CD, Weigert O, Peipp M, Schuendeln M, Stricker SH, Bernhagen J, Humpe A, Klump H, Brendel C, Krause DS, Greif PA, and Wichmann C (2024). Engineering an inducible leukemia-associated transcription factor enables large-scale ex vivo production of functional human phagocytes. PNAS 18;121(25):e2312499121 10.1073/pnas.2312499121
Simões S , Lino M, Barrera A, Rebelo C, Tomatis F, Vilaça A, Breunig C, Neuner A, Peça J, González R, Carvalho A, Gotz M, Stricker SH, Ferreira L (2024). Near infrared light-activated formulation for the spatial controlled release of CRISPR-Cas9 ribonucleoprotein for brain gene editing. Angewandte Chemie 21;63(21):e202401004 10.1002/anie.202401004
Stricker, SH (2023). Folding makes an imprint .Genes and Development 1;37(17-18):779-780 10.1101/gad.351216.123
Hersbach B, Fischer DS, Masserdotti G, Deeksha, Mojžišová K, Waltzhöni T, Rodriguez-Terrones D, Heinig M, Theis FJ, Götz M, Stricker SH (2022) Probing cell identity hierarchies by fate titration and collision during direct reprogramming.Molecular Systems Biology 18(9):e11129. 10.15252/msb.202211129
Sanchez-Gonzalez R, Koupourtidou C, Lepko T, Zambusi A, Novoselc KT, Durovic T, Aschenbroich S, Schwarz V, Breunig CT, Straka H, Huttner HB, Irmler M, Beckers J, Wurst W, Zwergal A, Schauer T, Straub T, Czopka T, Trümbach D, Götz M, Stricker SH, Ninkovic J. (2022) Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain.Cells 2;11(3):520. 10.3390/cells11030520
Stricker SH, Berninger B, Götz M. (2021) Editorial overview: Fluidity of cell fates - from reprogramming to repair.Curr Opin Genet Dev. 70:iii-v. 10.1016/j.gde.2021.08.001
Breunig CT, Koferle A, Neuner AM, Wiesbeck MF, Baumann V, Stricker SH (2021) CRISPR Tools for Physiology and Cell State Changes: Potential of Transcriptional Engineering and Epigenome Editing.Physiol Rev 101: 177-211 10.1152/physrev.00034.2019
Russo G, Sonsalla G, Breunig C, Merl-Pham J, Schmitt S, Jastroch M, Zischka H, Stricker SH, Hauck MS, Masserdotti G et al (2021) CRISPR-mediated induction of neuron-enriched mitochondrial proteins boosts direct glia-to-neuron conversion.Cell Stem Cell28 (3): 524-534. 10.1016/j.stem.2020.10.015
Stricker SH, Götz M. (2021) Epigenetic regulation of neural lineage elaboration: Implications for therapeutic reprogramming. Neurobiol Dis. 148:105174. 10.1016/j.nbd.2020.105174
Baumann V, Wiesbeck M, Breunig CT, Braun JM, Koferle A, Ninkovic J, Gotz M, Stricker SH (2019) Targeted removal of epigenetic barriers during transcriptional reprogramming.Nature communications 10: 2119 10.1038/s41467-019-10146-8
Baumann V, Stricker SH. (2019) Seeking fate-CRISPRa screens reveal new neural lineage and reprogramming factors.Stem Cell Investig. 9;6:30. 10.21037/sci.2019.08.03
Lepko T, Pusch M, Muller T, Schulte D, Ehses J, Kiebler M, Hasler J, Huttner HB, Stricker SH, Gotz M, Ninkovic J (2019) Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.EMBO J: e100481 10.15252/embj.2018100481
Singh HR, Stricker SH. (2019) Glucose-Regulated TET2 Activity Links Cancer to Diabetes.Trends Cancer 5(1):5-7. 10.1016/j.trecan.2018.10.008
Breunig CT, Durovic T, Neuner AM, Baumann V, Wiesbeck MF, Koferle A, Gotz M, Ninkovic J, Stricker SH (2018) One step generation of customizable gRNA vectors for multiplex CRISPR approaches through string assembly gRNA cloning (STAgR).PLoS One 13: e0196015 10.1371/journal.pone.0196015
Di Giaimo R, Durovic T, Barquin P, Kociaj A, Lepko T, Aschenbroich S, Breunig CT, Irmler M, Stricker SH, Ninkovic J (2018) The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis. Cell Rep 25: 3241-3251 e3245 10.1016/j.celrep.2018.11.055
Breunig CT, Neuner AM, Giehrl-Schwab J, Wurst W, Götz M, Stricker SH. (2018) A Customizable Protocol for String Assembly gRNA Cloning (STAgR). J Vis Exp. 26;(142). 10.3791/58556
Stricker SH, Gotz M (2018)DNA-Methylation: Master or Slave of Neural Fate Decisions?Front Neurosci 12: 5 10.3389/fnins.2018.00005
Maher GJ, Ralph HK, Ding Z, Koelling N, Mlcochova H, Giannoulatou E, Dhami P, Paul DS, Stricker SH, Beck S, McVean G, Wilkie AOM, Goriely A. (2018) Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes. Genome Res 28(12):1779-1790. 10.1101/gr.239186.118
Bultmann S, Stricker SH. (2018) Entering the post-epigenomic age: back to epigenetics. Open Biol 8(3):180013. 10.1098/rsob.180013
Stricker SH, Koferle A, Beck S (2017) From profiles to function in epigenomics. Nat Rev Genet 18: 51-66 10.1038/nrg.2016.138
Köferle A, Stricker SH. (2017) A Universal Protocol for Large-scale gRNA Library Production from any DNA Source. J Vis Exp. 6;(130):56264. 10.3791/56264
Koferle A, Worf K, Breunig C, Baumann V, Herrero J, Wiesbeck M, Hutter LH, Gotz M, Fuchs C, Stricker SH (2016) CORALINA: a universal method for the generation of gRNA libraries for CRISPR-based screening.BMC Genomics 17: 91 10.1186/s12864-016-3268-z
Blake SM, Stricker SH, Halavach H, Poetsch AR, Cresswell G, Kelly G, Kanu N, Marino S, Luscombe NM, Pollard SM, Behrens A. (2016) Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation.Elife 17;5:e08711. 10.7554/eLife.08711
Carén H, Stricker SH, Bulstrode H, Gagrica S, Johnstone E, Bartlett TE, Feber A, Wilson G, Teschendorff AE, Bertone P, Beck S, Pollard SM. (2015) Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest. Stem Cell Reports 10;5(5):829-842. 10.1016/j.stemcr.2015.09.014
Danovi D, Folarin A, Gogolok S, Ender C, Elbatsh AM, Engström PG, Stricker SH, Gagrica S, Georgian A, Yu D, U KP, Harvey KJ, Ferretti P, Paddison PJ, Preston JE, Abbott NJ, Bertone P, Smith A, Pollard SM. (2013) A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One. 30;8(10):e77053. 10.1371/journal.pone.0077053
Stricker S, Pollard S. (2014) Reprogramming cancer cells to pluripotency: an experimental tool for exploring cancer epigenetics.Epigenetics. 9(6):798-802. 10.4161/epi.28600
Stricker SH, Feber A, Engström PG, Carén H, Kurian KM, Takashima Y, Watts C, Way M, Dirks P, Bertone P, Smith A, Beck S, Pollard SM. (2013) Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner. Genes Dev. 15;27(6):654-69. 10.1101/gad.212662.112
Latos PA, Pauler FM, Koerner MV, Şenergin HB, Hudson QJ, Stocsits RR, Allhoff W, Stricker SH, Klement RM, Warczok KE, Aumayr K, Pasierbek P, Barlow DP (2012) Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing.Science 14;338(6113):1469-72. 10.1126/science.1228110
Engström PG, Tommei D, Stricker SH, Ender C, Pollard SM, Bertone P. (2012) Digital transcriptome profiling of normal and glioblastoma-derived neural stem cells identifies genes associated with patient survival. Genome Med 9;4(10):76. 10.1186/gm377
Koerner MV, Pauler FM, Hudson QJ, Santoro F, Sawicka A, Guenzl PM, Stricker SH, Schichl YM, Latos PA, Klement RM, Warczok KE, Wojciechowski J, Seiser C, Kralovics R, Barlow DP (2012) A downstream CpG island controls transcript initiation and elongation and the methylation state of the imprinted Airn macro ncRNA promoter. PLoS Genet 8(3):e1002540. 10.1371/journal.pgen.1002540
Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, Bayani J, Head R, Lee M, Bernstein M, Squire JA, Smith A, Dirks P. (2009) Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell. 4(6):568-80. 10.1016/j.stem.2009.03.014
Pollard SM, Stricker SH, Beck S. (2009) Preview. A shore sign of reprogramming.Cell Stem Cell 4;5(6):571-2. 10.1016/j.stem.2009.11.006
Latos PA*, Stricker SH*, Steenpass L, Pauler FM, Huang R, Senergin BH, Regha K, Koerner MV, Warczok KE, Unger C, Barlow DP (2009) An in vitro ES cell imprinting model shows that imprinted expression of the Igf2r gene arises from an allele-specific expression bias. Development 136(3):437-48. 10.1242/dev.032060
Stricker SH, Steenpass L, Pauler FM, Santoro F, Latos PA, Huang R, Koerner MV, Sloane MA, Warczok KE, Barlow DP (2008) Silencing and transcriptional properties of the imprinted Airn ncRNA are independent of the endogenous promoter. EMBO J 3;27(23):3116-28. 10.1038/emboj.2008.239
Seidl CI*, Stricker SH*, Barlow DP (2006) The imprinted Air ncRNA is an atypical RNAPII transcript that evades splicing and escapes nuclear export.EMBO J. 9;25(15):3565-75. 10.1038/sj.emboj.7601245
Stricker SH, Meiri K, Götz M.(2006) P-GAP-43 is enriched in horizontal cell divisions throughout rat cortical development. Cereb Cortex. 16 Suppl 1:i121-31. 10.1093/cercor/bhj171
Götz M, Stricker SH. (2006) Go with the flow: signaling from the ventricle directs neuroblast migration. Nat Neurosci. 9(4):470-2. 10.1038/nn0406-470
Pauler FM, Stricker SH, Warczok KE, Barlow DP. (2005) Long-range DNase I hypersensitivity mapping reveals the imprinted Igf2r and Air promoters share cis-regulatory elements. Genome Res. 15(10):1379-87. 10.1101/gr.3783805