Joint profiling of chromatin accessibility and gene expression in thousands of single cells

Junyue Cao; Darren A. Cusanovich; Vijay Ramani; Delasa Aghamirzaie; Hannah A. Pliner; Andrew J. Hill; Riza M. Daza; Jose L. McFaline-Figueroa; Jonathan S. Packer; Lena Christiansen; Frank J. Steemers; Andrew Adey; Cole Trapnell; Jay Shendure

doi:10.1126/science.aau0730(2018)

Joint profiling of chromatin accessibility and gene expression in thousands of single cells

Junyue Cao, Darren A. Cusanovich, Vijay Ramani, Delasa Aghamirzaie, Hannah A. Pliner, Andrew J. Hill, Riza M. Daza, Jose L. McFaline-Figueroa, Jonathan S. Packer, Lena Christiansen, Frank J. Steemers, Andrew Adey, Cole Trapnell, Jay Shendure

Molecular & Medical Genetics

Research output: Contribution to journal › Article

2 Scopus citations

Abstract

Although we can increasingly measure transcription, chromatin, methylation, etc. at single cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing-based co-assay that jointly profiles chromatin accessibility and mRNA in each of thousands of single cells. As a proof-of-concept, we apply sci-CAR to 4,825 cells comprising a time-series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney. With the resulting data, we compare the pseudotemporal dynamics of chromatin accessibility and gene expression, reconstruct the chromatin accessibility profiles of cell types defined by RNA profiles, and link cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells.

Original language	English (US)
Journal	Science
DOIs	https://doi.org/10.1126/science.aau0730(2018)
State	Accepted/In press - Jan 1 2018

ASJC Scopus subject areas

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Cao, J., Cusanovich, D. A., Ramani, V., Aghamirzaie, D., Pliner, H. A., Hill, A. J., Daza, R. M., McFaline-Figueroa, J. L., Packer, J. S., Christiansen, L., Steemers, F. J., Adey, A., Trapnell, C., & Shendure, J. (Accepted/In press). Joint profiling of chromatin accessibility and gene expression in thousands of single cells. Science. https://doi.org/10.1126/science.aau0730(2018)

Joint profiling of chromatin accessibility and gene expression in thousands of single cells. / Cao, Junyue; Cusanovich, Darren A.; Ramani, Vijay; Aghamirzaie, Delasa; Pliner, Hannah A.; Hill, Andrew J.; Daza, Riza M.; McFaline-Figueroa, Jose L.; Packer, Jonathan S.; Christiansen, Lena; Steemers, Frank J.; Adey, Andrew; Trapnell, Cole; Shendure, Jay.

In: Science, 01.01.2018.

Research output: Contribution to journal › Article

Cao, Junyue ; Cusanovich, Darren A. ; Ramani, Vijay ; Aghamirzaie, Delasa ; Pliner, Hannah A. ; Hill, Andrew J. ; Daza, Riza M. ; McFaline-Figueroa, Jose L. ; Packer, Jonathan S. ; Christiansen, Lena ; Steemers, Frank J. ; Adey, Andrew ; Trapnell, Cole ; Shendure, Jay. / Joint profiling of chromatin accessibility and gene expression in thousands of single cells. In: Science. 2018.

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abstract = "Although we can increasingly measure transcription, chromatin, methylation, etc. at single cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing-based co-assay that jointly profiles chromatin accessibility and mRNA in each of thousands of single cells. As a proof-of-concept, we apply sci-CAR to 4,825 cells comprising a time-series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney. With the resulting data, we compare the pseudotemporal dynamics of chromatin accessibility and gene expression, reconstruct the chromatin accessibility profiles of cell types defined by RNA profiles, and link cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells.",

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AU - Hill, Andrew J.

AU - Daza, Riza M.

AU - McFaline-Figueroa, Jose L.

AU - Packer, Jonathan S.

AU - Christiansen, Lena

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AU - Adey, Andrew

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AU - Shendure, Jay

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