scholarly journals Unique Epigenetic Programming Distinguishes Regenerative Spermatogonial Stem Cells in the Developing Mouse Testis

2019 ◽  
Author(s):  
Keren Cheng ◽  
I-Chung Chen ◽  
Benjamin J. Hale ◽  
Brian P. Hermann ◽  
Christopher B. Geyer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Regenerative Capacity ◽  
Encode Project ◽  
Epigenetic Programming ◽  
Histone Modification Patterns

AbstractSpermatogonial stem cells (SSCs) both self-renew and give rise to progenitor spermatogonia that enter steady-state spermatogenesis in the mammalian testis. However, questions remain regarding the extent to which SSCs and progenitors represent stably distinct spermatogonial subtypes. Here we provide the first multiparametric integrative analysis of mammalian germ cell epigenomes comparable to that done by the ENCODE Project for >100 somatic cell types. Differentially expressed genes distinguishing SSCs and progenitors showed distinct histone modification patterns as well as differences in distal intergenic low-methylated regions. Motif-enrichment analysis predicted transcription factors that regulate this spermatogonial subtype-specific epigenetic programming, and gene-specific chromatin immunoprecipitation analyses confirmed subtype-specific differences in binding of a subset of these factors to target genes. Collectively, these results suggest that SSCs and progenitors are stably distinct spermatogonial subtypes differentially programmed to either self-renew and maintain regenerative capacity as SSCs, or lose regenerative capacity and initiate lineage commitment as progenitors.

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

2020 ◽  
Vol 21 (23) ◽  
pp. 9052
Author(s):  
Indrek Teino ◽  
Antti Matvere ◽  
Martin Pook ◽  
Inge Varik ◽  
Laura Pajusaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Target Genes ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
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.

scholarly journals HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

2019 ◽  
Vol 20 (22) ◽  
pp. 5815 ◽  
Author(s):  
Kovács ◽  
Sigmond ◽  
Hotzi ◽  
Bohár ◽  
Fazekas ◽  
...  
Keyword(s):  
Heat Shock ◽  
High Throughput ◽  
Ribosome Biogenesis ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Genes Encoding ◽  
Shock Proteins

: HSF1 (heat shock factor 1) is an evolutionarily conserved master transcriptional regulator of the heat shock response (HSR) in eukaryotic cells. In response to high temperatures, HSF1 upregulates genes encoding molecular chaperones, also called heat shock proteins, which assist the refolding or degradation of damaged intracellular proteins. Accumulating evidence reveals however that HSF1 participates in several other physiological and pathological processes such as differentiation, immune response, and multidrug resistance, as well as in ageing, neurodegenerative demise, and cancer. To address how HSF1 controls these processes one should systematically analyze its target genes. Here we present a novel database called HSF1Base (hsf1base.org) that contains a nearly comprehensive list of HSF1 target genes identified so far. The list was obtained by manually curating publications on individual HSF1 targets and analyzing relevant high throughput transcriptomic and chromatin immunoprecipitation data derived from the literature and the Yeastract database. To support the biological relevance of HSF1 targets identified by high throughput methods, we performed an enrichment analysis of (potential) HSF1 targets across different tissues/cell types and organisms. We found that general HSF1 functions (targets are expressed in all tissues/cell types) are mostly related to cellular proteostasis. Furthermore, HSF1 targets that are conserved across various animal taxa operate mostly in cellular stress pathways (e.g., autophagy), chromatin remodeling, ribosome biogenesis, and ageing. Together, these data highlight diverse roles for HSF1, expanding far beyond the HSR.

Effects of different Sertoli cell types on the maintenance of adult spermatogonial stem cells in vitro

2017 ◽  
Vol 53 (8) ◽  
pp. 752-758 ◽  
Author(s):  
Maryam Baazm ◽  
Farideh Jalali Mashayekhi ◽  
Saeid Babaie ◽  
Parvindokht Bayat ◽  
Cordian Beyer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sertoli Cell ◽  
Cell Types ◽  
Spermatogonial Stem Cells

scholarly journals EAT-UpTF: Enrichment Analysis Tool for Upstream Transcription Fctors of a gene group

2020 ◽  
Author(s):  
Sangrea Shim ◽  
Pil Joon Seo
Keyword(s):  
Transcription Factors ◽  
Open Source ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Affinity Purification ◽  
Enrichment Analysis ◽  
Analysis Tool ◽  
Gene Group ◽  
Genome Wide ◽  
One Step

SummaryEAT-UpTF (Enrichment Analysis Tool for Upstream Transcription Factors of a gene group) is an open-source Python script that analyzes the enrichment of upstream transcription factors (TFs) in a group of genes-of-interest (GOIs). EAT-UpTF utilizes genome-wide lists of TF-target genes generated by DNA affinity purification followed by sequencing (DAP-seq) or chromatin immunoprecipitation followed by sequencing (ChIP-seq). Unlike previous methods based on the two-step prediction of cis-motifs and DNA-element-binding TFs, our EAT-UpTF analysis enabled a one-step identification of enriched upstream TFs in a set of GOIs using lists of empirically determined TF-target [email protected] or [email protected]://github.com/sangreashim/EAT-UpTF

scholarly journals Expression of Promyelocytic Leukemia (PML) Protein in the Mouse Developing Spermatogonia

2020 ◽  
Author(s):  
Amin Tavassoli ◽  
Hesam DEHGHANI
Keyword(s):  
Stem Cells ◽  
Immunohistochemical Analysis ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Seminiferous Tubules ◽  
Open Chromatin ◽  
Pml Nuclear Bodies ◽  
Oct4 Protein

Abstract Background: Promyelocytic leukemia (PML) as the main protein of PML nuclear bodies regulates various physiological processes such as transcription, DNA repair, apoptosis, senescence, and several signaling pathways in different cell types. It is well known that the PML protein is involved in the regulation of stem cell properties by maintaining an open chromatin conformation for the regulatory regions of the Oct4 gene. However, there is no experimental evidence for the presence and function of PML protein in the testis tissue. Results: In this study, we show the presence of PML protein in the developing mouse testis and its co-expression with the OCT4 protein. Immunohistochemical analysis of testis mirror sections shows that PML is co-expressed with the OCT4 protein in the outermost cellular layer of seminiferous tubules, where the spermatogonial stem cells are located. Conclusions: Our findings suggest that the PML protein might be involved in the stemness of spermatogonial stem cells at different stages of its development, even before earning the ability to produce mature sperm.

234. Hedgehog signalling components in adult rat testis spermatogonial cells

2008 ◽  
Vol 20 (9) ◽  
pp. 34
Author(s):  
Z. Sahin ◽  
M. Meistrich ◽  
A. Szczepny ◽  
K. Loveland
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
In Situ Hybridisation ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Male Rats ◽  
Brown Norway ◽  
Hedgehog Signalling ◽  
Rat Testis ◽  
Adult Rat

In normal tissues, Hedgehog-induced progenitor cell proliferation is transient and tightly regulated, preventing continuous regeneration. However, activation of constitutive Hedgehog signalling results in unregulated self-renewal of progenitor cells in association with several human cancers. Although the contribution of Hedgehog signalling to cancers is widely accepted, its impact on spermatogonial stem cells and impact on male fertility are unknown. In this study, we aimed to clarify the possible role of Hh signalling on normal spermatogenesis in the adult rat and in adult testicular stem cells in the irradiated model {1}. Adult male rats were obtained from Monash University Central Animal Service and killed by cervical dislocation before tissue removal and fixation in Bouins for routine histochemical procedures. For studies on irradiated testes, adult LBNF1 male rats (hybrids between Lewis and Brown–Norway) were purchased from Harlan Sprague–Dawley, Inc. (Indianapolis, IN, USA). Testes were irradiated with 6 Gy to deplete all maturing germ cell types. At 15 weeks after irradiation the animals were injected simultaneously with 1.5 mg each of Cetrorelix pamoate and Cetrorelix acetate. Testes were collected 1, 2 or 4 weeks after injection. In situ hybridisation combined with immunohistochemistry was performed using DIG-labelled cRNA probes to identify the cells in which Hedgehog signalling components are made {2}. Signals for mRNAs encoding t he transmembrane receptors Ptc2 and Smo are most intensely detected in spermatogonia and spermatocytes and are much less intense in the round spermatids. The mRNA for the cytoplamic regulator, Fused, is restricted to the earliest germ cell types, whereas expression of the negative cytoplasmic regulator, SuFu, only begins in the round spermatids and persists in elongating spermatids. Gli1 and Gli3 are expressed from spermatogonia through to round spermatids, whereas Gli2 is restricted to spermatogonia and spermatocytes. This pattern mimics what was reported for mouse {2}. Examination of the irradiated rat testis model revealed that Hedgehog signalling machinery is produced by resting spermatogonial stem cells but is turned off when they differentiate in response to hormones. This matches the emerging understanding of Hedgehog signals in cancer stem cells and provides the first demonstration that Hedgehog signalling may influence stem cells in the adult testis. (1) Shuttlesworth G.A. et al. 2000. Endocrinology. 141: 37–49 (2) Szczepny A. et al. 2006. Dev Dyn. 235:3063–3070.

scholarly journals Roles of p53 in Various Biological Aspects of Hematopoietic Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Takenobu Nii ◽  
Tomotoshi Marumoto ◽  
Kenzaburo Tani
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cell Types ◽  
Cell Integrity ◽  
Hematopoietic Stem ◽  
Cycle Arrest ◽  
Successful Transplantation ◽  
Cellular Stresses

Hematopoietic stem cells (HSCs) have the capacity to self-renew as well as to differentiate into all blood cell types, and they can reconstitute hematopoiesis in recipients with bone marrow ablation. In addition, transplantation therapy using HSCs is widely performed for the treatment of various incurable diseases such as hematopoietic malignancies and congenital immunodeficiency disorders. For the safe and successful transplantation of HSCs, their genetic and epigenetic integrities need to be maintained properly. Therefore, understanding the molecular mechanisms that respond to various cellular stresses in HSCs is important. The tumor suppressor protein, p53, has been shown to play critical roles in maintenance of “cell integrity” under stress conditions by controlling its target genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In this paper, we summarize recent reports that describe various biological functions of HSCs and discuss the roles of p53 associated with them.

scholarly journals Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingyi Chen ◽  
Yuxuan Song ◽  
Mei Li ◽  
Yu Zhang ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Target Genes ◽  
Immune Cell ◽  
Pearson Correlation ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cerna Network

Abstract Background Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. Methods RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. Results A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. Conclusions MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.

scholarly journals Unique Epigenetic Programming Distinguishes Regenerative Spermatogonial Stem Cells in the Developing Mouse Testis

iScience ◽  
2020 ◽  
Vol 23 (10) ◽  
pp. 101596 ◽  
Author(s):  
Keren Cheng ◽  
I-Chung Chen ◽  
Ching-Hsun Eric Cheng ◽  
Kazadi Mutoji ◽  
Benjamin J. Hale ◽  
...  
Keyword(s):  
Stem Cells ◽  
Spermatogonial Stem Cells ◽  
Mouse Testis ◽  
Epigenetic Programming

scholarly journals Bioinformatics Analysis of Transcriptomic Data Reveals Refined Functional Networks for the Self-Renewal of Mouse Spermatogonial Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Min Wang ◽  
Wene Zhao ◽  
Fuqiang Wang ◽  
Xiufeng Ling ◽  
Daozhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Bioinformatics Analysis ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Expression Index ◽  
Extrinsic Factors ◽  
Self Renewal ◽  
Proliferation And Differentiation ◽  
Disease Associations

Spermatogonial stem cells (SSCs) are exquisitely regulated to reach a balance between proliferation and differentiation in the niche of seminiferous epithelium. Several extrinsic factors such as GDNF are reported to switch the transition, activating various intrinsic signaling pathways. Transcriptomics analysis could provide a comprehensive landscape of gene expression and regulation. Here, we reanalyzed a previously published transcriptome of two cell types (standing for self-renewing and differentiating SSCs correspondingly). First, we proposed a new parameter, the expression index, to sort the genes considering both absolute and relative expression levels. Using a dynamic statistical model, we identified a list of 1119 candidate genes for SSC self-renewal with the best enrichment of canonical markers. Finally, based on interaction relations, we further optimized the list and constructed a refined network containing integrated information of interactions, expression alternations, biological functions, and disease associations. Further annotation of the 521 refined genes involved in the network revealed an enrichment of well-studied signaling pathways. We believe that the refined network could help us better understand the regulation of SSCs’ fates, as well as find novel regulators or targets for SSC self-renewal or preservation of male fertility.

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