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Identification of transcriptional and metabolic programs related to mammalian cell size

Miettinen, Teemu P. ; Pessa, Heli K.J. ; Caldez, Matias J. ; Fuhrer, Tobias ; Diril, M. Kasim ; Sauer, Uwe ; Kaldis, Philipp LU and Björklund, Mikael (2014) In Current Biology 24(6). p.598-608
Abstract

SummaryBackground 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.... (More)

SummaryBackground 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.

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author
publishing date
type
Contribution to journal
publication status
published
in
Current Biology
volume
24
issue
6
pages
598 - 608
publisher
Elsevier
external identifiers
  • scopus:84896548332
  • pmid:24613310
ISSN
0960-9822
DOI
10.1016/j.cub.2014.01.071
language
English
LU publication?
no
id
537c389a-ca3c-4552-889a-5e7b8f2040e4
date added to LUP
2019-09-18 10:20:52
date last changed
2020-05-31 06:49:15
@article{537c389a-ca3c-4552-889a-5e7b8f2040e4,
  abstract     = {<p>SummaryBackground 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.</p>},
  author       = {Miettinen, Teemu P. and Pessa, Heli K.J. and Caldez, Matias J. and Fuhrer, Tobias and Diril, M. Kasim and Sauer, Uwe and Kaldis, Philipp and Björklund, Mikael},
  issn         = {0960-9822},
  language     = {eng},
  month        = {03},
  number       = {6},
  pages        = {598--608},
  publisher    = {Elsevier},
  series       = {Current Biology},
  title        = {Identification of transcriptional and metabolic programs related to mammalian cell size},
  url          = {http://dx.doi.org/10.1016/j.cub.2014.01.071},
  doi          = {10.1016/j.cub.2014.01.071},
  volume       = {24},
  year         = {2014},
}