Perturbing the UPR: Single-cell CRISPRi screens interrogate the unfolded protein response
Britt Adamson, PhD
Wednesday, November 29, 2017
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Chapters
Introduction
The Unfolded Protein Response is a branched stress signaling network with diverse inputs
Traditional approaches for evaluating transcriptional programs require a complexity tradeoff
Pooled CRISPRi screening by single-cell RNA-seq: Perturb-seq
CRISPRi screening by droplet-based single-cell RNA-seq: Perturb-seq
How to capture perturbation identity within single-cell transcriptomes?
sgRNA identity mapping is robust
1. What can Perturb-seq can do?
Clustering hit genes by correlation of bulk expression profiles reveals functional relationships
2. Waht can Perturb-seq can do?
Systematic decoupling of transcriptional circuits: Perturb-seq after repression of three UPR arms
Decoupling of transcriptional programs with single-cell data
Decoupling of transcriptional programs with single-cell data using low rank independent component analysis
Decoupling transcriptional programs within Perturb-seq data from UPR-inducing sublibrary
3. Waht can Perturb-seq can do?
Do individual cells execute a heterogeneous UPR in response to homogeneous perturbation?
exploring single-cell UPR induction in response to BiP depletion
Recap: What can Perturb-seq can do?
Acknowledgements
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