CRISPR Technology Maps Every Human Gene Function
Whitehead Institute researchers have created the first information-rich genotype-phenotype map that reveals a multidimensional portrait of gene and cellular function. By performing genome-scale Perturb-seq (CRISPR-based screens with single-cell RNA-sequencing readouts) targeting all expressed genes in millions of human cells, Jonathan Weissman, PhD, and colleagues have mapped the transcriptional effects of genetic perturbations to predict the function of genes at genome-scale.
There are few questions more fundamental to genetics and other fields of biology than, “What is the function of every gene?” Researchers have chipped away at this problem for decades, first by dissecting individual genes to more recent advances with genome-wide approaches like Perturb-seq, albeit at limited scales.
Sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.
The Whitehead researchers turned this concept on its head, using Perturb-seq to reveal a multidimensional portrait of cellular behavior, gene function, and regulatory networks.
The genome-phenotype maps were able to pry open the longstanding question of why mitochondria still have their own DNA. The analysis revealed how nuclear and mitochondrial DNA are coordinated and regulated in different cellular conditions, especially when a cell is stressed.
To conclude the article, Weissman and colleagues emphasized that single-cell CRISPR screens require only a fraction of the number of cells used by other approaches and thus are well suited to the study of iPSC-derived cells and in vivo samples. At present, the major limitation of single-cell CRISPR screens is cost.
https://www.genengnews.com/crispr/crispr-technology-maps-every-human-gene-function/
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