Abstract：
:Finding the components of cellular circuits and determining their functions systematically remains a major challenge in mammalian cells. Here, we introduced genome-wide pooled CRISPR-Cas9 libraries into dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (Tnf) by bacterial lipopolysaccharide (LPS), a key process in the host response to pathogens, mediated by the Tlr4 pathway. We found many of the known regulators of Tlr4 signaling, as well as dozens of previously unknown candidates that we validated. By measuring protein markers and mRNA profiles in DCs that are deficient in known or candidate genes, we classified the genes into three functional modules with distinct effects on the canonical responses to LPS and highlighted functions for the PAF complex and oligosaccharyltransferase (OST) complex. Our findings uncover new facets of innate immune circuits in primary cells and provide a genetic approach for dissection of mammalian cell circuits.
journal_name
Celljournal_title
Cellauthors
Parnas O,Jovanovic M,Eisenhaure TM,Herbst RH,Dixit A,Ye CJ,Przybylski D,Platt RJ,Tirosh I,Sanjana NE,Shalem O,Satija R,Raychowdhury R,Mertins P,Carr SA,Zhang F,Hacohen N,Regev Adoi
10.1016/j.cell.2015.06.059subject
Has Abstractpub_date
2015-07-30 00:00:00pages
675-86issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00829-6journal_volume
162pub_type
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