Dynamic regulation of mitochondrial function in preimplantation embryos and embryonic stem cells

Harvey, Alexandra J; Gibson, Tiffini C.; Lonergan, Thomas A.; Brenner, Carol A.

doi:10.1016/j.mito.2010.12.013

Cited by 32 publications

(27 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We did find that the cells had perinuclear located mitochondria, and the transcriptome profiling of mitochondrial dynamic related genes also verified significantly higher level of fission gene Mff expression, and significantly lower expression levels of fusion genes including Mfn1 , Mfn2 and Opa1 , which might explain mitochondrial fusion defects and mitochondrial fragmentation in these cells. Recent studies have illustrated that mitochondria dynamic balance exhibits tendentiousness towards to fission during the metabolic reprograming by cell pluripotent maintenance [53, 57]. MJ Son et al have further demonstrated that blocking Mfn gene, which regulates mitochondrial fussion is favorable for pluripotency inducement [45].…”

Section: Discussionmentioning

confidence: 99%

MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

Lü

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features.

show abstract

Section: Discussionmentioning

confidence: 99%

MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

Lü

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Mitochondria are responsible for the vital regulation of cellular homeostasis through the metabolism of respiratory substrate, OXPHOS, ion homeostasis, ROS production, and apoptosis [13,35]. Several lines of investigation have suggested the possible associations of high-potential mitochondria with the ability of matured oocytes to be fertilized and the developmental competence of postfertilization embryos [9,49,51].…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria regulate cellular homeostasis, including the metabolism of respiratory substrates, oxidative phosphorylation (OXPHOS), ion homeostasis, reactive oxygen species (ROS) production, and apoptosis [13,35]. The critical roles of mitochondria in mammalian oogenesis and early embryogenesis are emerging as a correlation to developmental outcome in oocyte maturation, fertilization, and postfertilization development [9,49,51].…”

Section: Introductionmentioning

confidence: 99%

Astaxanthin ameliorates heat stress-induced impairment of blastocyst development In Vitro: –astaxanthin colocalization with and action on mitochondria–

Kuroki

Ikeda

Okada

et al. 2013

J Assist Reprod Genet

View full text Add to dashboard Cite

show abstract

“…mtDNA content is known to be a major determinant of mitochondrial gene expression [43]. Undifferentiated mouse and human ES cells have very low levels of mtDNA content (<100 copies/cell), but this rapidly increases up to several thousand-fold during differentiation [44][45][46][47]. However, it remains to be determined whether human iPS cells are able, like ES cells, to regulate their mtDNA copy number in their undifferentiated state.…”

Section: Discussionmentioning

confidence: 99%

Induced pluripotent stem cells generated from diabetic patients with mitochondrial DNA A3243G mutation

et al. 2012

View full text Add to dashboard Cite

Aims/hypothesis The aim of this study was to generate induced pluripotent stem (iPS) cells from patients with mitochondrial DNA (mtDNA) mutation. Methods Skin biopsies were obtained from two diabetic patients with mtDNA A3243G mutation. The fibroblasts thus obtained were infected with retroviruses encoding OCT4 (also known as POU5F1), SOX2, c-MYC (also known as MYC) and KLF4. The stem cell characteristics were investigated and the mtDNA mutation frequencies evaluated by Invader assay.Results From the two diabetic patients we isolated four and ten putative mitochondrial disease-specific iPS (Mt-iPS) clones, respectively. Mt-iPS cells were cytogenetically normal and positive for alkaline phosphatase activity, with the pluripotent stem cell markers being detectable by immunocytochemistry. The cytosine guanine dinucleotide islands in the promoter regions of OCT4 and NANOG were highly unmethylated, indicating epigenetic reprogramming to pluripotency. Mt-iPS clones were able to differentiate into derivatives of all three germ layers in vitro and in vivo. The Mt-iPS cells exhibited a bimodal degree of mutation heteroplasmy. The mutation frequencies decreased to an undetectable level in six of 14 clones, while the others showed several-fold increases in mutation frequencies (51-87%) compared with those in the original fibroblasts (18-24%). During serial cell culture passage and after differentiation, no recurrence of the mutation or no significant changes in the levels of heteroplasmy were seen. Conclusions/interpretation iPS cells were successfully generated from patients with the mtDNA A3243G mutation. Mutation-rich, stable Mt-iPS cells may be a suitable source of cells for human mitochondrial disease modelling in vitro. Mutation-free iPS cells could provide an unlimited, diseasefree supply of cells for autologous transplantation therapy.

show abstract

Dynamic regulation of mitochondrial function in preimplantation embryos and embryonic stem cells

Cited by 32 publications

References 120 publications

MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

Astaxanthin ameliorates heat stress-induced impairment of blastocyst development In Vitro: –astaxanthin colocalization with and action on mitochondria–

Induced pluripotent stem cells generated from diabetic patients with mitochondrial DNA A3243G mutation

Contact Info

Product

Resources

About