Project Description

Z03: Experimental and computational single-cell sequencing

The focus will be on three sc-seq methods that are particularly informative for this purpose:
(i) Single cell RNA sequencing (scRNA-seq) to evaluate cellular heterogeneity and cell fate trajectories
(ii) single cell ATAC-seq (scATAC-seq) to map the heterogeneity of active regulatory elements and chromatin states as an additional “omics” layer linked to epigenetic differences and functional changes
(iii) a “spatially-resolved transcriptomics” (SRT) approach that links imaging-based information with the scRNA readout from the same single cell in order to reveal how the cellular context affects susceptibility and response towards infection
Al-Ali R, Bauer K, Park JW, Al Abdulla R, Fermi V, von Deimling A, Herold-Mende C, Mallm JP,
Herrmann C, Wick W, Turcan S. 2019. Single-nucleus chromatin accessibility reveals intratumoral epigenetic heterogeneity in IDH1 mutant gliomas. Acta Neuropathol Commun 7(1):201.
Liu L, Liu C, Quintero A, Wu L, Yuan Y, …, Chen F, Herrmann C, Eils R, Shang Z, Xu X. 2019. Deconvolu-tion of single-cell multi-omics layers reveals regulatory heterogeneity. Nat Comm. 10(1): 470.
Thier MC, Hommerding O, Panten J, Pinna R, García-González D, Berger T, …, Herrmann C, Monyer H, Edenhofer F, Trumpp A. 2019. Identification of Embryonic Neural Plate Border Stem Cells and Their Genera-tion by Direct Reprogramming from Adult Human Blood Cells. Cell Stem Cell. 24(1), 166-182.e13
Mallm JP, Iskar M, Ishaque N, Klett LC, Kugler SJ, …, Stilgenbauer S, Lichter P, Zapatka M, Mertens D, Rippe K. 2019. Linking aberrant chromatin features in chronic lymphocytic leukemia to deregulated tran-scription factor networks. Mol Syst Biol. 15(5): e8339.
Becker H, Greve G, Kataoka K, Mallm JP, Duque-Afonso J, …, Cleary ML, Schüler J, Rippe K, Ogawa S, Lübbert M. 2019. Identification of enhancer of mRNA decapping 4 as a novel fusion partner of MLL in acute myeloid leukemia. Blood Adv. 3(5):761-765
Zirkel A, Nikolic M, Sofiadis K, Mallm JP, Brackley CA, …, Roukos V, Nürnberg P, Marenduzzo D, Rippe K, Papantonis A. 2018. HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types. Mol Cell 70(4): 730-744.
Molitor J, Mallm JP, Rippe K*, Erdel F*. 2017. Retrieving Chromatin Patterns from Deep Sequencing Data Using Correlation Functions. Biophys J. 112: 473-490.
Delacher M, Imbusch CD, Weichenhan D, Breiling A, Hotz-Wagenblatt A, Träger U, Hofer AC, Kägebein D, Wang Q, Frauhammer F, Mallm JP, Bauer K, Herrmann C, Lang PA, Brors B, Plass C, Feuerer M. 2017. Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues. Nat Immu-nol. 18(10):1160-1172.
Bauer T, Trump S, Ishaque N, Thürmann L, Gu L, …, Rippe K, Mizuguchi J, Herrmann C*, Eils R*, Lehmann I*. 2016. Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking moth-ers and their children. Mol Syst Biol. 12(3):861.
Teif VB, Beshnova DA, Vainshtein Y, Marth C, Mallm JP, Höfer T, Rippe K. 2014. Nucleosome repositioning links DNA (de)methylation and differential CTCF binding during stem cell development. Genome Res. 24: 1285-1295