High-resolution characterization of gene function using single-cell CRISPR tiling screen

Lu Yang, Anthony K. N. Chan, Kazuya Miyashita, Christopher D. Delaney, Xi Wang, Hongzhi Li, Sheela Pangeni Pokharel, Sandra Li, Mingli Li, Xiaobao Xu, Wei Lu, Qiao Liu, Nicole Mattson, Kevin Yining Chen, Jinhui Wang, Yate-Ching Yuan, David Horne, Steven T. Rosen, Yadira Soto-Feliciano, Zhaohui Feng, Takayuki Hoshii, Gang Xiao, Markus Müschen, Jianjun Chen, Scott A. Armstrong () and Chun-Wei Chen ()
Additional contact information
Lu Yang: Beckman Research Institute
Anthony K. N. Chan: Beckman Research Institute
Kazuya Miyashita: Beckman Research Institute
Christopher D. Delaney: Dana-Farber Cancer Institute—Harvard Medical School
Xi Wang: Dana-Farber Cancer Institute—Harvard Medical School
Hongzhi Li: City of Hope Comprehensive Cancer Center
Sheela Pangeni Pokharel: Beckman Research Institute
Sandra Li: Beckman Research Institute
Mingli Li: Beckman Research Institute
Xiaobao Xu: Beckman Research Institute
Wei Lu: Beckman Research Institute
Qiao Liu: Beckman Research Institute
Nicole Mattson: Beckman Research Institute
Kevin Yining Chen: Dana-Farber Cancer Institute—Harvard Medical School
Jinhui Wang: City of Hope Comprehensive Cancer Center
Yate-Ching Yuan: City of Hope Comprehensive Cancer Center
David Horne: City of Hope Comprehensive Cancer Center
Steven T. Rosen: City of Hope Comprehensive Cancer Center
Yadira Soto-Feliciano: Rockefeller University
Zhaohui Feng: Dana-Farber Cancer Institute—Harvard Medical School
Takayuki Hoshii: Dana-Farber Cancer Institute—Harvard Medical School
Gang Xiao: Beckman Research Institute
Markus Müschen: Beckman Research Institute
Jianjun Chen: Beckman Research Institute
Scott A. Armstrong: Dana-Farber Cancer Institute—Harvard Medical School
Chun-Wei Chen: Beckman Research Institute

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via CRISPR tiling of gene-coding exons has been demonstrated to identify functional regions in genes. Furthermore, breakthroughs in combining CRISPR library screens with single-cell droplet RNA sequencing (sc-RNAseq) platforms have revealed the capacity to monitor gene expression changes upon genetic perturbations at single-cell resolution. Here, we present “sc-Tiling,” which integrates a CRISPR gene-tiling screen with single-cell transcriptomic and protein structural analyses. Distinct from other reported single-cell CRISPR screens focused on observing gene function and gene-to-gene/enhancer-to-gene regulation, sc-Tiling enables the capacity to identify regulatory mechanisms within a gene-coding region that dictate gene activity and therapeutic response.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24324-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24324-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24324-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().