4.7 Article

Trans-omics analysis of insulin action reveals a cell growth subnetwork which co-regulates anabolic processes

Journal

ISCIENCE
Volume 25, Issue 5, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2022.104231

Keywords

-

Funding

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [JP17H06300, JP17H06299, JP18H03979, JP21H04759]
  2. Japan Science and Technology Agency (JST) [JPMJCR2123]
  3. Uehara Memorial Foundation
  4. JSPS KAKENHI Grant [JP18H05431]
  5. NIA [R00 AG057792]
  6. National Institutes of Health [R01 AR057352, P01 CA120964, R01 DK088718]
  7. [JP21K16349]
  8. [JP21K15342]
  9. [JP17K14864]
  10. [JP21K14467]

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This study constructed a transgenic network to investigate the role of insulin in Drosophila cells. The findings suggest that insulin promotes cell growth and proliferation by regulating gene expression, especially genes involved in anabolic metabolism.
Insulin signaling promotes anabolic metabolism to regulate cell growth through multi-omic interactions. To obtain a comprehensive view of the cellular responses to insulin, we constructed a trans-omic network of insulin action in Drosophila cells that involves the integration ofmulti-omic data sets. In this network, 14 transcription factors, including Myc, coordinately upregulate the gene expression of anabolic processes such as nucleotide synthesis, transcription, and translation, consistent with decreases in metabolites such as nucleotide triphosphates and proteinogenic amino acids required for transcription and translation. Next, as cell growth is required for cell proliferation and insulin can stimulate proliferation in a context-dependent manner, we integrated the trans-omic network with results from a CRISPR functional screen for cell proliferation. This analysis validates the role of a Myc-mediated subnetwork that coordinates the activation of genes involved in anabolic processes required for cell growth.

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