Functional buffering via cell-specific gene expression promotes tissue homeostasis and cancer robustness

Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that func...

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Bibliographic Details
Published in:Scientific reports 2022-02, Vol.12 (1), p.2974-2974, Article 2974
Main Authors: Lin, Hao-Kuen, Cheng, Jen-Hao, Wu, Chia-Chou, Hsieh, Feng-Shu, Dunlap, Carolyn, Chen, Sheng-hong
Format: Article
Language:English
Subjects:
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Blood cells
CRISPR
Gene expression
Genomes
Homeostasis
Humanities and Social Sciences
multidisciplinary
Regeneration
Science
Science (multidisciplinary)
Tissues
Transcriptomics
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Summary:Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that functional buffering can be mediated via expression of buffering genes in specific cells and tissues, by which we named Cell-specific Expression-BUffering (CEBU). We developed an inference index (C-score) for CEBU by computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq. We report that C-score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results suggest CEBU as a potential buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-06813-4