Facucho-Oliveira, Joao M., Alderson, Jon, Spikings, Emma C., Egginton, Stuart and St. John, Justin C.. (2007) Mitochondrial DNA replication during differentiation of murine embryonic stem cells. Journal of Cell Science, Vol.120 (No.22). pp. 4025-4034. ISSN 0021-9533

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Abstract

Oxidative phosphorylation (OXPHOS), the intracellular process that generates the majority of the ATP of a cell through the electron-transfer chain, is highly dependent on proteins encoded by the mitochondrial genome ( mtDNA). MtDNA replication is regulated by the nuclear-encoded mitochondrial transcription factor A (TFAM) and the mitochondrial-specific DNA polymerase gamma, which consists of a catalytic (POLG) and an accessory (POLG2) subunit. Differentiation of pluripotent embryonic stem cells (ESCs) into specific cell types requires expansion of discrete populations of mitochondria and mtDNA replication to meet the specific metabolic requirements of the cell. We determined by real-time PCR that expression of pluripotent markers is reduced before the upregulation of Polg, Polg2 and Tfam in spontaneously differentiating R1 murine (m) ESCs, along with transient increases in mtDNA copy number. In D3 mESCs, the initial transient increase did not take place. However, precursors of neuronal and cardiomyocyte differentiation were positive for both POLG and TFAM. Similar-stage ESCs also showed active mtDNA replication, identified by 5-bromo-2'-deoxy-uridine labelling, as mtDNA copy number increased. Retinoic-acid-induced differentiation resulted in more consistent patterns of replication and upregulation of Polg, Polg2 and Tfam, whereas siRNA knockdown demonstrated that steady-state expression of POLG is essential for maintaining pluripotency.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Journal of Cell Science
Publisher:	The Company of Biologists Ltd.
ISSN:	0021-9533
Date:	15 November 2007
Volume:	Vol.120
Number:	No.22
Number of Pages:	10
Page Range:	pp. 4025-4034
Identification Number:	10.1242/jcs.016972
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/31121

Data sourced from Thomson Reuters' Web of Knowledge

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