Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells
Abstract 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 thera...
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doaj-d89867322e804dd0acd2dc0180fe5fe82021-03-11T12:50:05ZengBMCGenome Biology1474-760X2021-03-0122111910.1186/s13059-021-02293-3Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cellsDrew Neavin0Quan Nguyen1Maciej S. Daniszewski2Helena H. Liang3Han Sheng Chiu4Yong Kiat Wee5Anne Senabouth6Samuel W. Lukowski7Duncan E. Crombie8Grace E. Lidgerwood9Damián Hernández10James C. Vickers11Anthony L. Cook12Nathan J. Palpant13Alice Pébay14Alex W. Hewitt15Joseph E. Powell16Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical ResearchInstitute for Molecular Bioscience, University of QueenslandCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalInstitute for Molecular Bioscience, University of QueenslandGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical ResearchGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical ResearchInstitute for Molecular Bioscience, University of QueenslandCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalWicking Dementia Research and Education Centre, University of TasmaniaWicking Dementia Research and Education Centre, University of TasmaniaInstitute for Molecular Bioscience, University of QueenslandCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical ResearchAbstract 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.https://doi.org/10.1186/s13059-021-02293-3Expression quantitative trait loci (eQTLs)Single cell RNA-sequencing (scRNA-seq)Induced pluripotent stem cells (iPSCs) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Drew Neavin Quan Nguyen Maciej S. Daniszewski Helena H. Liang Han Sheng Chiu Yong Kiat Wee Anne Senabouth Samuel W. Lukowski Duncan E. Crombie Grace E. Lidgerwood Damián Hernández James C. Vickers Anthony L. Cook Nathan J. Palpant Alice Pébay Alex W. Hewitt Joseph E. Powell |
spellingShingle |
Drew Neavin Quan Nguyen Maciej S. Daniszewski Helena H. Liang Han Sheng Chiu Yong Kiat Wee Anne Senabouth Samuel W. Lukowski Duncan E. Crombie Grace E. Lidgerwood Damián Hernández James C. Vickers Anthony L. Cook Nathan J. Palpant Alice Pébay Alex W. Hewitt Joseph E. Powell Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells Genome Biology Expression quantitative trait loci (eQTLs) Single cell RNA-sequencing (scRNA-seq) Induced pluripotent stem cells (iPSCs) |
author_facet |
Drew Neavin Quan Nguyen Maciej S. Daniszewski Helena H. Liang Han Sheng Chiu Yong Kiat Wee Anne Senabouth Samuel W. Lukowski Duncan E. Crombie Grace E. Lidgerwood Damián Hernández James C. Vickers Anthony L. Cook Nathan J. Palpant Alice Pébay Alex W. Hewitt Joseph E. Powell |
author_sort |
Drew Neavin |
title |
Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells |
title_short |
Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells |
title_full |
Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells |
title_fullStr |
Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells |
title_full_unstemmed |
Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells |
title_sort |
single cell eqtl analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2021-03-01 |
description |
Abstract 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. |
topic |
Expression quantitative trait loci (eQTLs) Single cell RNA-sequencing (scRNA-seq) Induced pluripotent stem cells (iPSCs) |
url |
https://doi.org/10.1186/s13059-021-02293-3 |
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