Related Experiment Video
Updated: May 15, 2026
09:03
Profiling Individual Human Embryonic Stem Cells by Quantitative RT-PCR
Published on: May 29, 2014
Mitochondrial DNA haplotypes define gene expression patterns in pluripotent and differentiating embryonic stem cells
Richard D W Kelly1, Andrew E Rodda, Adam Dickinson
1Mitochondrial Genetics Group, Centre for Reproduction and Development, Monash Institute of Medical ResearchMonash University, Clayton, Victoria, Australia.
Stem Cells (Dayton, Ohio)
|January 12, 2013
Summary
Mitochondrial DNA (mtDNA) haplotypes impact cell differentiation and development. Different mtDNA haplotypes influence gene expression and cardiomyocyte production in embryonic stem cells, revealing their crucial role in cell fate.
Area of Science:
- Genetics
- Developmental Biology
- Cell Biology
Background:
- Mitochondrial DNA (mtDNA) haplotypes are linked to diverse phenotypes, including disease susceptibility, adaptation, and aging.
- mtDNA is recognized as crucial for cell differentiation and phenotype, but its specific impact via different haplotypes on development is unclear.
Purpose of the Study:
- To investigate the effects of distinct mitochondrial DNA (mtDNA) haplotypes on chromosomal gene expression, differentiation, and mitochondrial metabolism in embryonic stem cells.
- To determine if mtDNA haplotypes influence the developmental potential of embryonic stem cells.
Main Methods:
- Utilized embryonic stem cell lines with identical chromosomes but varying mtDNA haplotypes (Mus musculus, Mus spretus, Mus terricolor).
- Analyzed gene expression patterns, differentiation capacity (cardiomyocyte production), and mitochondrial function (ATP, oxygen consumption, respiration).
- Examined gene expression in a 3D differentiation environment.
Main Results:
- Observed mtDNA haplotype-specific gene expression in pluripotency, differentiation, energy metabolism, and DNA methylation pathways.
- Found that mtDNA haplotypes influenced the ability of stem cells to form cardiomyocytes.
- These effects were independent of cellular bioenergetics (ATP, oxygen consumption, respiration).
- Haplotype-specific gene expression differences persisted even in a 3D differentiation environment.
Conclusions:
- Mitochondrial DNA haplotypes significantly influence chromosomal gene expression and embryonic stem cell differentiation.
- mtDNA haplotypes play a critical role in mediating cell fate and developmental processes, beyond their known roles in energy metabolism.
- These findings highlight the phenotypic consequences of mtDNA variation in development.
Related Concept Videos
01:14Maintenance of the ES Cell State
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
02:59Animal Mitochondrial Genetics
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
00:57Embryonic Stem Cells
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...