Identification of transcriptional and metabolic programs related to mammalian cell size

Teemu P. Miettinen, Heli K. J. Pessa, Matias J. Caldez, Tobias Fuhrer, M. Kasim Diril, Uwe Sauer, Philipp Kaldis, Mikael Bjorklund (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    48 Citations (Scopus)
    121 Downloads (Pure)

    Abstract

    Background
    Regulation of cell size requires coordination of growth and proliferation. Conditional loss of cyclin-dependent kinase 1 in mice permits hepatocyte growth without cell division, allowing us to study cell size in vivo using transcriptomics and metabolomics.

    Results
    Larger cells displayed increased expression of cytoskeletal genes but unexpectedly repressed expression of many genes involved in mitochondrial functions. This effect appears to be cell autonomous because cultured Drosophila cells induced to increase cell size displayed a similar gene-expression pattern. Larger hepatocytes also displayed a reduction in the expression of lipogenic transcription factors, especially sterol-regulatory element binding proteins. Inhibition of mitochondrial functions and lipid biosynthesis, which is dependent on mitochondrial metabolism, increased the cell size with reciprocal effects on cell proliferation in several cell lines.

    Conclusions
    We uncover that large cell-size increase is accompanied by downregulation of mitochondrial gene expression, similar to that observed in diabetic individuals. Mitochondrial metabolism and lipid synthesis are used to couple cell size and cell proliferation. This regulatory mechanism may provide a possible mechanism for sensing metazoan cell size.

    Original languageEnglish
    Pages (from-to)598-608
    Number of pages11
    JournalCurrent Biology
    Volume24
    Issue number6
    DOIs
    Publication statusPublished - Mar 2014

    Fingerprint Dive into the research topics of 'Identification of transcriptional and metabolic programs related to mammalian cell size'. Together they form a unique fingerprint.

  • Cite this

    Miettinen, T. P., Pessa, H. K. J., Caldez, M. J., Fuhrer, T., Diril, M. K., Sauer, U., Kaldis, P., & Bjorklund, M. (2014). Identification of transcriptional and metabolic programs related to mammalian cell size. Current Biology, 24(6), 598-608. https://doi.org/10.1016/j.cub.2014.01.071