Locus-specific Expression of Transposable Elements in Single Cells with CELLO-seq

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2021 Nov 16

PMID 34782740

Citations 25

Authors

Rebecca V Berrens

Andrian Yang

Christopher E Laumer

Aaron T L Lun

Florian Bieberich

Cheuk-Ting Law

Guocheng Lan

Maria Imaz

Joseph S Bowness

Neil Brockdorff

Daniel J Gaffney

John C Marioni

Affiliations

Soon will be listed here.

Abstract

Transposable elements (TEs) regulate diverse biological processes, from early development to cancer. Expression of young TEs is difficult to measure with next-generation, single-cell sequencing technologies because their highly repetitive nature means that short complementary DNA reads cannot be unambiguously mapped to a specific locus. Single CELl LOng-read RNA-sequencing (CELLO-seq) combines long-read single cell RNA-sequencing with computational analyses to measure TE expression at unique loci. We used CELLO-seq to assess the widespread expression of TEs in two-cell mouse blastomeres as well as in human induced pluripotent stem cells. Across both species, old and young TEs showed evidence of locus-specific expression with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to the reference with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed large heterogeneity, with TEs within a class showing different patterns of correlation and suggesting distinct regulatory mechanisms.

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References

Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K, Ashford S . Common genetic variation drives molecular heterogeneity in human iPSCs. Nature. 2017; 546(7658):370-375. PMC: 5524171. DOI: 10.1038/nature22403. View

Guenther M, Frampton G, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R . Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell. 2010; 7(2):249-57. PMC: 3010384. DOI: 10.1016/j.stem.2010.06.015. View

Garcia-Perez J, Widmann T, Adams I . The impact of transposable elements on mammalian development. Development. 2016; 143(22):4101-4114. PMC: 5830075. DOI: 10.1242/dev.132639. View

Lun A, Riesenfeld S, Andrews T, Dao T, Gomes T, Marioni J . EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. Genome Biol. 2019; 20(1):63. PMC: 6431044. DOI: 10.1186/s13059-019-1662-y. View

Wissing S, Munoz-Lopez M, Macia A, Yang Z, Montano M, Collins W . Reprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility. Hum Mol Genet. 2011; 21(1):208-18. PMC: 3235014. DOI: 10.1093/hmg/ddr455. View

Peaston A, Evsikov A, Graber J, de Vries W, Holbrook A, Solter D . Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell. 2004; 7(4):597-606. DOI: 10.1016/j.devcel.2004.09.004. View

Ribet D, Louvet-Vallee S, Harper F, de Parseval N, Dewannieux M, Heidmann O . Murine endogenous retrovirus MuERV-L is the progenitor of the "orphan" epsilon viruslike particles of the early mouse embryo. J Virol. 2007; 82(3):1622-5. PMC: 2224431. DOI: 10.1128/JVI.02097-07. View

Wu J, Huang B, Chen H, Yin Q, Liu Y, Xiang Y . The landscape of accessible chromatin in mammalian preimplantation embryos. Nature. 2016; 534(7609):652-7. DOI: 10.1038/nature18606. View

Percharde M, Lin C, Yin Y, Guan J, Peixoto G, Bulut-Karslioglu A . A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity. Cell. 2018; 174(2):391-405.e19. PMC: 6046266. DOI: 10.1016/j.cell.2018.05.043. View

10.

Picelli S, Faridani O, Bjorklund A, Winberg G, Sagasser S, Sandberg R . Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc. 2014; 9(1):171-81. DOI: 10.1038/nprot.2014.006. View

11.

Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E . Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA. Nat Struct Mol Biol. 2013; 20(3):332-8. DOI: 10.1038/nsmb.2495. View

12.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

13.

Pitkanen E, Cajuso T, Katainen R, Kaasinen E, Valimaki N, Palin K . Frequent L1 retrotranspositions originating from TTC28 in colorectal cancer. Oncotarget. 2014; 5(3):853-9. PMC: 3996660. DOI: 10.18632/oncotarget.1781. View

14.

Okae H, Chiba H, Hiura H, Hamada H, Sato A, Utsunomiya T . Genome-wide analysis of DNA methylation dynamics during early human development. PLoS Genet. 2014; 10(12):e1004868. PMC: 4263407. DOI: 10.1371/journal.pgen.1004868. View

15.

Philippe C, Vargas-Landin D, Doucet A, van Essen D, Vera-Otarola J, Kuciak M . Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci. Elife. 2016; 5. PMC: 4866827. DOI: 10.7554/eLife.13926. View

16.

Park S, Shirahige K, Ohsugi M, Nakai K . DBTMEE: a database of transcriptome in mouse early embryos. Nucleic Acids Res. 2014; 43(Database issue):D771-6. PMC: 4383872. DOI: 10.1093/nar/gku1001. View

17.

Hoang M, Kinde I, Tomasetti C, McMahon K, Rosenquist T, Grollman A . Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing. Proc Natl Acad Sci U S A. 2016; 113(35):9846-51. PMC: 5024639. DOI: 10.1073/pnas.1607794113. View

18.

Ge S . Exploratory bioinformatics investigation reveals importance of "junk" DNA in early embryo development. BMC Genomics. 2017; 18(1):200. PMC: 5324221. DOI: 10.1186/s12864-017-3566-0. View

19.

Jachowicz J, Bing X, Pontabry J, Boskovic A, Rando O, Torres-Padilla M . LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo. Nat Genet. 2017; 49(10):1502-1510. DOI: 10.1038/ng.3945. View

20.

Boroviak T, Stirparo G, Dietmann S, Hernando-Herraez I, Mohammed H, Reik W . Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development. Development. 2018; 145(21). PMC: 6240320. DOI: 10.1242/dev.167833. View