Role of laminin and collagen chains in human spermatogenesis – Insights from studies in rodents and scRNA-Seq transcriptome profiling

2021 ◽  
Author(s):  
Xiaolong Wu ◽  
Sheng Gao ◽  
Lingling Wang ◽  
Tiao Bu ◽  
Siwen Wu ◽  
...  
Keyword(s):  
Transcriptome Profiling ◽  
Human Spermatogenesis

scholarly journals Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer

2018 ◽  
Vol 111 (7) ◽  
pp. 664-674 ◽  
Author(s):  
Rongqiang Yang ◽  
Steven W Li ◽  
Zirong Chen ◽  
Xin Zhou ◽  
Wei Ni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcriptome Profiling ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Growth And Survival ◽  
Cancer Genome Atlas ◽  
Lung Adenocarcinomas ◽  
Genome Atlas

Abstract Background The LKB1 tumor suppressor gene is commonly inactivated in non-small cell lung carcinomas (NSCLC), a major form of lung cancer. Targeted therapies for LKB1-inactivated lung cancer are currently unavailable. Identification of critical signaling components downstream of LKB1 inactivation has the potential to uncover rational therapeutic targets. Here we investigated the role of INSL4, a member of the insulin/IGF/relaxin superfamily, in LKB1-inactivated NSCLCs. Methods INSL4 expression was analyzed using global transcriptome profiling, quantitative reverse transcription PCR, western blotting, enzyme-linked immunosorbent assay, and RNA in situ hybridization in human NSCLC cell lines and tumor specimens. INSL4 gene expression and clinical data from The Cancer Genome Atlas lung adenocarcinomas (n = 515) were analyzed using log-rank and Fisher exact tests. INSL4 functions were studied using short hairpin RNA (shRNA) knockdown, overexpression, transcriptome profiling, cell growth, and survival assays in vitro and in vivo. All statistical tests were two-sided. Results INSL4 was identified as a novel downstream target of LKB1 deficiency and its expression was induced through aberrant CRTC-CREB activation. INSL4 was highly induced in LKB1-deficient NSCLC cells (up to 543-fold) and 9 of 41 primary tumors, although undetectable in all normal tissues except the placenta. Lung adenocarcinomas from The Cancer Genome Atlas with high and low INSL4 expression (with the top 10th percentile as cutoff) showed statistically significant differences for advanced tumor stage (P < .001), lymph node metastasis (P = .001), and tumor size (P = .01). The INSL4-high group showed worse survival than the INSL4-low group (P < .001). Sustained INSL4 expression was required for the growth and viability of LKB1-inactivated NSCLC cells in vitro and in a mouse xenograft model (n = 5 mice per group). Expression profiling revealed INSL4 as a critical regulator of cell cycle, growth, and survival. Conclusions LKB1 deficiency induces an autocrine INSL4 signaling that critically supports the growth and survival of lung cancer cells. Therefore, aberrant INSL4 signaling is a promising therapeutic target for LKB1-deficient lung cancers.

scholarly journals picd-1, a gene that encodes CABIN1 domain-containing protein, interacts with pry-1/Axin to regulate multiple processes in Caenorhabditis elegans

2021 ◽  
Author(s):  
Avijit Mallick ◽  
Shane K. B. Taylor ◽  
Sakshi Mehta ◽  
Bhagwati P. Gupta
Keyword(s):  
Stress Response ◽  
Essential Role ◽  
Family Members ◽  
Transcriptome Profiling ◽  
Scaffolding Protein ◽  
Dependent Manner ◽  
C Elegans ◽  
Downstream Effectors ◽  
Cellular Components

ABSTRACTAXIN family members control diverse biological processes in eukaryotes. As a scaffolding protein, AXIN facilitates interactions between cellular components and provides specificity to signaling pathways. Despite its crucial roles in metazoans and discovery of a large number of family members, the mechanism of AXIN function is not very well understood. The C. elegans AXIN homolog PRY-1 provides a powerful tool to identify interacting genes and downstream effectors that function in a conserved manner to regulate AXIN-mediated signaling. Previous work demonstrated pry-1’s essential role in developmental processes such as reproductive system, seam cells, and a P lineage cell P11.p. More recently, our lab carried out a transcriptome profiling of pry-1 mutant and uncovered the essential role of the gene in lipid metabolism, stress response, and aging. In this study, we have extended the work on pry-1 by reporting a novel interacting gene picd-1 (pry-1-interacting CABIN1 domain containing). Our findings have revealed that picd-1 plays an essential role in C. elegans and is involved in several pry-1-mediated processes including regulation of stress response and lifespan maintenance. In support of this, picd-1 expression overlaps with pry-1 in multiple tissues throughout the lifespan of animals. Further experiments showed that picd-1 inhibits CREB-regulated transcriptional coactivator homolog CRTC-1 function, which promotes longevity in a calcineurin-dependent manner. These data provide evidence for an essential role of the CABIN1 domain protein PICD-1 in mediating PRY-1 signaling in C. elegans.

scholarly journals Toxin-Antitoxin Systems in Escherichia coli Influence Biofilm Formation through YjgK (TabA) and Fimbriae

2008 ◽  
Vol 191 (4) ◽  
pp. 1258-1267 ◽  
Author(s):  
Younghoon Kim ◽  
Xiaoxue Wang ◽  
Qun Ma ◽  
Xue-Song Zhang ◽  
Thomas K. Wood
Keyword(s):  
Biofilm Formation ◽  
Cell Attachment ◽  
Single Gene ◽  
Transcriptome Profiling ◽  
Uncharacterized Protein ◽  
Qrt Pcr ◽  
Biofilm Dispersal ◽  
Biofilm Development ◽  
Whole Transcriptome

ABSTRACT The roles of toxin-antitoxin (TA) systems in bacteria have been debated. Here, the role of five TA systems in regard to biofilm development was investigated (listed as toxin/antitoxin: MazF/MazE, RelE/RelB, ChpB, YoeB/YefM, and YafQ/DinJ). Although these multiple TA systems were reported previously to not impact bacterial fitness, we found that deletion of the five TA systems decreased biofilm formation initially (8 h) on three different surfaces and then increased biofilm formation (24 h) by decreasing biofilm dispersal. Whole-transcriptome profiling revealed that the deletion of the five TA systems induced expression of a single gene, yjgK, which encodes an uncharacterized protein; quantitative real-time PCR (qRT-PCR) confirmed consistent induction of this gene (at 8, 15, and 24 h). Corroborating the complex phenotype seen upon deleting the TA systems, overexpression of YjgK decreased biofilm formation at 8 h and increased biofilm formation at 24 h; deletion of yjgK also affected biofilm formation in the expected manner by increasing biofilm formation after 8 h and decreasing biofilm formation after 24 h. In addition, YjgK significantly reduced biofilm dispersal. Whole-transcriptome profiling revealed YjgK represses fimbria genes at 8 h (corroborated by qRT-PCR and a yeast agglutination assay), which agrees with the decrease in biofilm formation upon deleting the five TA systems at 8 h, as well as that seen upon overexpressing YjgK. Sand column assays confirmed that deleting the five TA systems reduced cell attachment. Furthermore, deletion of each of the five toxins increased biofilm formation at 8 h, and overexpression of the five toxins repressed biofilm formation at 8 h, a result that is opposite that of deleting all five TA systems; this suggests that complex regulation occurs involving the antitoxins. Also, the ability of the global regulator Hha to reduce biofilm formation was dependent on the presence of these TA systems. Hence, we suggest that one role of TA systems is to influence biofilm formation.

scholarly journals Transcriptome profiling analysis reveals the role of silique in controlling seed oil content in Brassica napus

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0179027 ◽  
Author(s):  
Ke-Lin Huang ◽  
Mei-Li Zhang ◽  
Guang-Jing Ma ◽  
Huan Wu ◽  
Xiao-Ming Wu ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Oil Content ◽  
Seed Oil ◽  
Transcriptome Profiling ◽  
Seed Oil Content ◽  
Profiling Analysis

ORIGINAL ARTICLE: The Role of IL-6, IL-10, TNF-α and its Receptors TNFR1 and TNFR2 in the Local Regulatory System of Normal and Impaired Human Spermatogenesis

2009 ◽  
Vol 62 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Małgorzata Białas ◽  
Dorota Fiszer ◽  
Natalia Rozwadowska ◽  
Włodzimierz Kosicki ◽  
Piotr Jedrzejczak ◽  
...  
Keyword(s):  
Regulatory System ◽  
Tnf Α ◽  
Human Spermatogenesis

scholarly journals Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition

2020 ◽  
Author(s):  
Luis Enrique Cabrera Quio ◽  
Alexander Schleiffer ◽  
Karl Mechtler ◽  
Andrea Pauli
Keyword(s):  
Regulation Of Gene Expression ◽  
Physiological Role ◽  
Transcriptome Profiling ◽  
Time Frame ◽  
Rna Degradation ◽  
Developmental Transitions ◽  
Mrna Targets ◽  
Go Enrichment ◽  
Normal Adults

AbstractPost-transcriptional mechanisms are crucial for the regulation of gene expression. These mechanisms are particularly important during rapid developmental transitions such as the oocyte-to-embryo transition, which is characterized by dramatic changes to the developmental program in the absence of nuclear transcription. Under these conditions, changes to the RNA content are solely dependent on RNA degradation. Although several mechanisms that promote RNA decay during embryogenesis have been identified, it remains unclear which cellular machineries contribute to remodeling the maternal transcriptome during the oocyte-to-embryo transition. Here, we focused on the auxiliary 3’-to-5’ degradation factor Ski7 in zebrafish as its mRNA peaks during this time frame. Homozygous ski7 mutant fish were viable and developed into morphologically normal adults, yet they had decreased fertility. Consistent with the idea that Ski7 participates in remodeling the transcriptome during the oocyte-to-embryo transition, transcriptome profiling identified stage-specific mRNA targets of Ski7. Genes upregulated in ski7 mutants were generally lowly expressed in wild type, suggesting that Ski7 maintains low transcript levels for this subset of genes. GO enrichment analyses of genes mis-regulated in ski7 mutants implicated Ski7 in the regulation of redox processes. This was confirmed experimentally by an increased resistance of ski7 mutant embryos to reductive stress. Overall, our results provide first insights into the physiological role of vertebrate Ski7 as an important post-transcriptional regulator during the oocyte-to-embryo transition.

scholarly journals Neuroendocrine Modulation Sustains the C. elegans Forward Motor State

2016 ◽  
Author(s):  
Maria A. Lim ◽  
Jyothsna Chitturi ◽  
Valeriya Laskova ◽  
Jun Meng ◽  
Daniel Findeis ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Transcriptome Profiling ◽  
Behavioral State ◽  
Forward Movement ◽  
C Elegans ◽  
Peptidergic Neuron ◽  
Homeobox Transcription Factor

AbstractNeuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14. RID activity increases during forward movement. Ablating RID reduces the sustainability of forward movement, a phenotype partially recapitulated by removing FLP-14. Optogenetic depolarization of RID prolongs forward movement, an effect reduced in the absence of FLP-14. Together, these results establish the role of a neuroendocrine cell RID in sustaining a specific behavioral state in C. elegans.

scholarly journals The H3.3K27M oncohistone antagonizes reprogramming in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (7) ◽  
pp. e1009225
Author(s):  
Kami Ahmad ◽  
Steven Henikoff
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Transcriptome Profiling ◽  
Master Regulator ◽  
Developmental Program ◽  
Histone H3k27 ◽  
Chromatin Profiling ◽  
Development Proceeds ◽  
Simple Combination

Development proceeds by the activation of genes by transcription factors and the inactivation of others by chromatin-mediated gene silencing. In certain cases development can be reversed or redirected by mis-expression of master regulator transcription factors. This must involve the activation of previously silenced genes, and such developmental aberrations are thought to underlie a variety of cancers. Here, we express the wing-specific Vestigial master regulator to reprogram the developing eye, and test the role of silencing in reprogramming using an H3.3K27M oncohistone mutation that dominantly inhibits histone H3K27 trimethylation. We find that production of the oncohistone blocks eye-to-wing reprogramming. CUT&Tag chromatin profiling of mutant tissues shows that H3K27me3 of domains is generally reduced upon oncohistone production, suggesting that a previous developmental program must be silenced for effective transformation. Strikingly, Vg and H3.3K27M synergize to stimulate overgrowth of eye tissue, a phenotype that resembles that of mutations in Polycomb silencing components. Transcriptome profiling of elongating RNA Polymerase II implicates the mis-regulation of signaling factors in overgrowth. Our results demonstrate that growth dysregulation can result from the simple combination of crippled silencing and transcription factor mis-expression, an effect that may explain the origins of oncohistone-bearing cancers.

scholarly journals The role of retinoic acid in hepatic lipid homeostasis defined by genomic binding and transcriptome profiling

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 575 ◽  
Author(s):  
Yuqi He ◽  
Lei Gong ◽  
Yaping Fang ◽  
Qi Zhan ◽  
Hui-Xin Liu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Transcriptome Profiling ◽  
Lipid Homeostasis ◽  
Hepatic Lipid
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