scholarly journals Comparative analysis of the mitochondrial morphology, energy metabolism, and gene expression signatures in three types of blastocyst-derived stem cells

Redox Biology ◽  
2020 ◽  
Vol 30 ◽  
pp. 101437 ◽  
Author(s):  
Joonhyuk Choi ◽  
Bong Jong Seo ◽  
Hyeonwoo La ◽  
Sang Hoon Yoon ◽  
Yean Ju Hong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Comparative Analysis ◽  
Energy Metabolism ◽  
Mitochondrial Morphology ◽  
Gene Expression Signatures

An in silico screen links gene expression signatures to drug response in glioblastoma stem cells

2014 ◽  
Vol 15 (4) ◽  
pp. 347-353 ◽  
Author(s):  
G Riddick ◽  
H Song ◽  
S L Holbeck ◽  
W Kopp ◽  
J Walling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
In Silico ◽  
Drug Response ◽  
Glioblastoma Stem Cells ◽  
Gene Expression Signatures

scholarly journals Changes in the Expression of Mitochondrial Morphology-Related Genes during the Differentiation of Murine Embryonic Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Jeong Eon Lee ◽  
Bong Jong Seo ◽  
Min Ji Han ◽  
Yean Ju Hong ◽  
Kwonho Hong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Mitochondrial Fission ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Cell Types ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Stems Cells

During embryonic development, cells undergo changes in gene expression, signaling pathway activation/inactivation, metabolism, and intracellular organelle structures, which are mediated by mitochondria. Mitochondria continuously switch their morphology between elongated tubular and fragmented globular via mitochondrial fusion and fission. Mitochondrial fusion is mediated by proteins encoded by Mfn1, Mfn2, and Opa1, whereas mitochondrial fission is mediated by proteins encoded by Fis1 and Dnm1L. Here, we investigated the expression patterns of mitochondria-related genes during the differentiation of mouse embryonic stem cells (ESCs). Pluripotent ESCs maintain stemness in the presence of leukemia inhibitory factor (LIF) via the JAK-STAT3 pathway but lose pluripotency and differentiate in response to the withdrawal of LIF. We analyzed the expression levels of mitochondrial fusion- and fission-related genes during the differentiation of ESCs. We hypothesized that mitochondrial fusion genes would be overexpressed while the fission genes would be downregulated during the differentiation of ESCs. Though the mitochondria exhibited an elongated morphology in ESCs differentiating in response to LIF withdrawal, only the expression of Mfn2 was increased and that of Dnm1L was decreased as expected, the other exceptions being Mfn1, Opa1, and Fis1. Next, by comparing gene expression and mitochondrial morphology, we proposed an index that could precisely represent mitochondrial changes during the differentiation of pluripotent stem cells by analyzing the expression ratios of three fusion- and two fission-related genes. Surprisingly, increased Mfn2/Dnm1L ratio was correlated with elongation of mitochondria during the differentiation of ESCs. Moreover, application of this index to other specialized cell types revealed that neural stems cells (NSCs) and mouse embryonic fibroblasts (MEFs) showed increased Mfn2/Dnm1L ratio compared to ESCs. Thus, we suggest that the Mfn2/Dnm1L ratio could reflect changes in mitochondrial morphology according to the extent of differentiation.

scholarly journals Oocyte developmental failure in response to elevated nonesterified fatty acid concentrations: mechanistic insights

Reproduction ◽  
2013 ◽  
Vol 145 (1) ◽  
pp. 33-44 ◽  
Author(s):  
V Van Hoeck ◽  
J L M R Leroy ◽  
M Arias Alvarez ◽  
D Rizos ◽  
A Gutierrez-Adan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Ovarian Follicle ◽  
Developmental Competence ◽  
Nonesterified Fatty Acid ◽  
Mitochondrial Morphology ◽  
Functional Perspective ◽  
Expression Of Genes ◽  
Mitochondrial Fatty Acid

Elevated plasma nonesterified fatty acid (NEFA) concentrations are associated with negative energy balance and metabolic disorders such as obesity and type II diabetes. Such increased plasma NEFA concentrations induce changes in the microenvironment of the ovarian follicle, which can compromise oocyte competence. Exposing oocytes to elevated NEFA concentrations during maturation affects the gene expression and phenotype of the subsequent embryo, notably prompting a disrupted oxidative metabolism. We hypothesized that these changes in the embryo are a consequence of modified energy metabolism in the oocyte. To investigate this, bovine cumulus oocyte complexes were matured under elevated NEFA conditions, and energy metabolism-related gene expression, mitochondrial function, and ultrastructure evaluated. It was found that expression of genes related to REDOX maintenance was modified in NEFA-exposed oocytes, cumulus cells, and resultant blastocysts. Moreover, the expression of genes related to fatty acid synthesis in embryos that developed from NEFA-exposed oocytes was upregulated. From a functional perspective, inhibition of fatty acid β-oxidation in maturing oocytes exposed to elevated NEFA concentrations restored developmental competence. There were no clear differences in mitochondrial morphology or oxygen consumption between treatments, although there was a trend for a higher mitochondrial membrane potential in zygotes derived from NEFA-exposed oocytes. These data show that the degree of mitochondrial fatty acid β-oxidation has a decisive impact on the development of NEFA-exposed oocytes. Furthermore, the gene expression data suggest that the resulting embryos adapt through altered metabolic strategies, which might explain the aberrant energy metabolism previously observed in these embryos originating from NEFA-exposed maturing oocytes.

scholarly journals Oct1/Pou2f1 is selectively required for gut regeneration and regulates gut malignancy

2018 ◽  
Author(s):  
Karina Vázquez-Arreguín ◽  
Claire Bensard ◽  
John C. Schell ◽  
Eric Swanson ◽  
Xinjian Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Colon Cancer ◽  
Transcription Factor ◽  
Stem Cell ◽  
The United States ◽  
Mitotic Stability ◽  
Cell Compartments ◽  
Incidence And Mortality ◽  
Gene Expression Signatures

AbstractThe transcription factor Oct1/Pou2f1 promotes poised gene expression states, mitotic stability, glycolytic metabolism and other characteristics of stem cell potency. To determine the effect of Oct1 loss on stem cell maintenance and malignancy, we deleted Oct1 in two different mouse gut stem cell compartments. Oct1 deletion preserved homeostasis in vivo and the ability to generate cultured organoids in vitro, but blocked the ability to regenerate after treatment with dextran sodium sulfate, and the ability to maintain organoids after passage. In a chemical model of colon cancer, loss of Oct1 in the colon severely restricted tumorigenicity. In contrast, loss of one or bothOct1alleles progressively increased tumor burden in a colon cancer model driven by loss of heterozygosity of the tumor suppressor geneApc.The different outcomes are consistent with prior findings that Oct1 promotes mitotic stability, and consistent with different gene expression signatures associated with the two models. These results reveal that Oct1 is selectively required for gut regeneration, and has potent effects in colon malignancy, with outcome (pro-oncogenic or tumor suppressive) dictated by tumor etiology.Author summaryColorectal cancer is the second leading cause of cancer death in the United States. Approximately 35% of diagnosed patients eventually succumb to disease. The high incidence and mortality due to colon cancer demand a better understanding of factors controlling the physiology and pathophysiology of the gastrointestinal tract. Previously, we and others showed that the widely expressed transcription factor is expressed at higher protein levels in stem cells, including intestinal stem cells. In this study we use a conditional mouseOct1(Pou2f1) allele deleted in two different intestinal stem cell compartments. The results indicate that Oct1 loss is dispensable for maintenance of the mouse gut, but required for regeneration. We also tested Oct1 loss in the context of two different mouse colon cancer models. We find that Oct1 loss has opposing effects in the two models, and further that the two models are associated with different gene expression signatures. The differentially expressed genes are enriched for previously identified Oct1 targets, suggesting that differential gene control by Oct1 is one mechanism underlying different outcomes.

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