Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells.

Autor:	Neavin D; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia., Nguyen Q; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., Daniszewski MS; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia.; Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia., Liang HH; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia., Chiu HS; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., Wee YK; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia., Senabouth A; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia., Lukowski SW; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., Crombie DE; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia., Lidgerwood GE; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia.; Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia., Hernández D; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia.; Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia., Vickers JC; Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Australia., Cook AL; Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Australia., Palpant NJ; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., Pébay A; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia.; Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia., Hewitt AW; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.; Department of Surgery, The University of Melbourne, Melbourne, Australia.; School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., Powell JE; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia. j.powell@garvan.org.au.; UNSW Cellular Genomics Futures Institute, School of Medical Sciences, University of New South Wales, Sydney, Australia. j.powell@garvan.org.au.
Jazyk:	angličtina
Zdroj:	Genome biology [Genome Biol] 2021 Mar 05; Vol. 22 (1), pp. 76. Date of Electronic Publication: 2021 Mar 05.
DOI:	10.1186/s13059-021-02293-3
Abstrakt:	Background: The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) has provided a foundation for in vitro human disease modelling, drug development and population genetics studies. Gene expression plays a critical role in complex disease risk and therapeutic response. However, while the genetic background of reprogrammed cell lines has been shown to strongly influence gene expression, the effect has not been evaluated at the level of individual cells which would provide significant resolution. By integrating single cell RNA-sequencing (scRNA-seq) and population genetics, we apply a framework in which to evaluate cell type-specific effects of genetic variation on gene expression. Results: Here, we perform scRNA-seq on 64,018 fibroblasts from 79 donors and map expression quantitative trait loci (eQTLs) at the level of individual cell types. We demonstrate that the majority of eQTLs detected in fibroblasts are specific to an individual cell subtype. To address if the allelic effects on gene expression are maintained following cell reprogramming, we generate scRNA-seq data in 19,967 iPSCs from 31 reprogramed donor lines. We again identify highly cell type-specific eQTLs in iPSCs and show that the eQTLs in fibroblasts almost entirely disappear during reprogramming. Conclusions: This work provides an atlas of how genetic variation influences gene expression across cell subtypes and provides evidence for patterns of genetic architecture that lead to cell type-specific eQTL effects.
Databáze:	MEDLINE
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