Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types.

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MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells

Journal of Translational Medicine ◽

10.1186/1479-5876-7-20 ◽

2009 ◽

Vol 7 (1) ◽

pp. 20 ◽

Cited By ~ 118

Author(s):

Jiaqiang Ren ◽

Ping Jin ◽

Ena Wang ◽

Francesco M Marincola ◽

David F Stroncek

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Expression Patterns ◽

Embryonic Stem ◽

Gene Expression Patterns

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

Stem Cells International ◽

10.1155/2020/9369268 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 2

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.

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Human Embryonic Stem Cells (hESCs) Cultured Under Distinctive Feeder-Free Culture Conditions Display Global Gene Expression Patterns Similar to hESCs from Feeder-Dependent Culture Conditions

Stem Cell Reviews and Reports ◽

10.1007/s12015-010-9158-x ◽

2010 ◽

Vol 6 (3) ◽

pp. 425-437 ◽

Cited By ~ 14

Author(s):

Tae-Min Yoon ◽

Bomi Chang ◽

Hyeung-Taek Kim ◽

Joo-Hyun Jee ◽

Dong-Wook Kim ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Expression Patterns ◽

Embryonic Stem ◽

Global Gene Expression ◽

Culture Conditions ◽

Gene Expression Patterns

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Changes in the expression of mitochondrial morphology-related genes during the differentiation of murine embryonic stem cells

10.1101/644906 ◽

2019 ◽

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

AbstractDuring 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 Dmn1L. Here, we investigated the expression patterns of mitochondria-related genes during the differentiation of mouse embryonic stem cells (ESCs) in response to leukemia inhibitory factor (LIF) withdrawal. The expression of Mfn2 and Dnm1L was, as expected, increased and decreased, respectively. 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.

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CD34+CD38- hematopoietic precursors derived from human embryonic stem cells exhibit an embryonic gene expression pattern

Blood ◽

10.1182/blood-2003-10-3575 ◽

2004 ◽

Vol 103 (11) ◽

pp. 4134-4141 ◽

Cited By ~ 45

Author(s):

Shi-Jiang Lu ◽

Fei Li ◽

Loyda Vida ◽

George R. Honig

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Fetal Liver ◽

Expression Patterns ◽

Embryonic Stem ◽

Gene Expression Pattern ◽

Early Developmental Stage ◽

In Cells

Abstract Gene expression patterns of CD34+CD38- cells derived from human embryonic stem cells (ESCs) were compared with those of cells isolated from adult human bone marrow (BM) using microarrays; 1692 and 1494 genes were expressed at levels at least 3-fold above background in cells from BM and ESCs, respectively. Of these, 494 showed similar levels of expression in cells from both sources, 791 genes were overexpressed in cells from BM (BM versus ESCs, at least 2-fold), and 803 genes were preferentially expressed in cells from ESCs (ESCs versus BM, at least 2-fold). The message of the flt-3 gene was markedly decreased in cells from ESCs, whereas there was substantial flt-3 expression in cells from BM. High levels of embryonic ϵ-globin expression were observed—but no adult β-globin message—in CD34+CD38- cells from ESCs, whereas high levels of β-globin expression—but no embryonic ϵ-globin message—could be detected in cells from BM. Furthermore, high levels of major histocompatibility complex (MHC) gene expression were demonstrated in cells from BM but very low levels of MHC message in corresponding cells from ESCs. These observations demonstrate that CD34+CD38- cells derived from ESCs correspond consistently to an early developmental stage at which the yolk sac and fetal liver are the primary sites of hematopoiesis.

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