In our group we are interested in shedding light on central molecular processes in human cells, in particular with regards to the control of alternative splicing of transcribed mRNAs.
For this, we develop and employ cutting edge single-cell sequencing and computational approaches.
Pre-messenger RNAs of transcribed genes are subject to alternative splicing in over 90% of multi-exon protein coding genes in the human body and correct choice of isoforms is key for cell differentiation, development and response to extracellular cues. There is currently little in-depth understanding on the usage of alternative splice isoforms to control cellular identities and it frequently remains unclear how cells mediate the exact expression of particular isoforms.
In order to better understand the patterns of alternative splicing and the underlying mechanisms that cells may employ to control them, we utilize modern single-cell genomics technologies. We develop and improve in particular full-length transcriptome sequencing to open up new possibilities to study this exciting topic. We hope that this technology development leads us to generate a deep and genome-wide mechanistic understanding of alternative splicing regulation, with important implications for many diseases where splicing has been observed to be altered.
In this area, a particular interest of the lab lies in splicing of pre-mRNA which is frequently dysregulated in cancers, especially in hematologic malignancies with recurrent somatic mutations of the spliceosome. Here, we envision that we can contribute to discovery of new targets for personalized therapies with our unique perspective of single-cell splicing analyses.
Do you want to join our research group?
Interested and motivated persons are always welcome to contact us! If you want to join or mission or maybe apply for a grant together, feel free to contact us at firstname.lastname@example.org.
We are glad to have generous support from:
- Karolinska Institutet
- The Department of Medical Biochemistry and Biophysics (MBB)
- Åke Wibergs Stiftelse
Scalable single-cell RNA sequencing from full transcripts with Smart-seq3xpress.
Hagemann-Jensen M, Ziegenhain C, Sandberg R
Nat Biotechnol 2022 Oct;40(10):1452-1457
Molecular spikes: a gold standard for single-cell RNA counting.
Ziegenhain C, Hendriks GJ, Hagemann-Jensen M, Sandberg R
Nat Methods 2022 May;19(5):560-566
BAMboozle removes genetic variation from human sequence data for open data sharing.
Ziegenhain C, Sandberg R
Nat Commun 2021 Oct;12(1):6216
Transcriptional kinetics and molecular functions of long noncoding RNAs.
Johnsson P, Ziegenhain C, Hartmanis L, Hendriks GJ, Hagemann-Jensen M, Reinius B, Sandberg R
Nat Genet 2022 Mar;54(3):306-317
Single-cell RNA counting at allele and isoform resolution using Smart-seq3.
Hagemann-Jensen M, Ziegenhain C, Chen P, Ramsköld D, Hendriks GJ, Larsson AJM, Faridani OR, Sandberg R
Nat Biotechnol 2020 Jun;38(6):708-714
zUMIs - A fast and flexible pipeline to process RNA sequencing data with UMIs.
Parekh S, Ziegenhain C, Vieth B, Enard W, Hellmann I
Gigascience 2018 Jun;7(6)
Comparative Analysis of Single-Cell RNA Sequencing Methods.
Ziegenhain C, Vieth B, Parekh S, Reinius B, Guillaumet-Adkins A, Smets M, Leonhardt H, Heyn H, Hellmann I, Enard W
Mol Cell 2017 Feb;65(4):631-643.e4
Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia.
Ebinger S, Özdemir EZ, Ziegenhain C, Tiedt S, Castro Alves C, Grunert M, Dworzak M, Lutz C, Turati VA, Enver T, Horny HP, Sotlar K, Parekh S, Spiekermann K, Hiddemann W, Schepers A, Polzer B, Kirsch S, Hoffmann M, Knapp B, Hasenauer J, Pfeifer H, Panzer-Grümayer R, Enard W, Gires O, Jeremias I
Cancer Cell 2016 Dec;30(6):849-862