scholarly journals Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rupalatha Maddala ◽  
Junyuan Gao ◽  
Richard T. Mathias ◽  
Tylor R. Lewis ◽  
Vadim Y. Arshavsky ◽  
...  

AbstractS100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of the ocular lens and that S100A4(−/−) knockout mice develop late-onset cortical cataracts. Transcriptome profiling of lenses from S100A4(−/−) mice revealed a robust increase in the expression of multiple photoreceptor- and Müller glia-specific genes, as well as the olfactory sensory neuron-specific gene, S100A5. This aberrant transcriptional profile is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of differentially expressed genes in S100A4(−/−) lenses identified Crx and Nrl transcription factors as the most significant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high-density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this finding, we further documented that S100A4(−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, our findings suggest that S100A4 suppresses the expression of retinal genes during lens differentiation plausibly via a mechanism involving changes in histone methylation.

2019 ◽  
Author(s):  
Bei LI ◽  
Xiaolong He ◽  
Yiping Zhao ◽  
Dongyi Bai ◽  
Ming Du ◽  
...  

Abstract Introduction: The development of horse testis and spermatogenesis is a complex physiological process. Methods: To study those physiological processes, 3 immature and 3 mature testes of Mongolian horse were collected, and six libraries were established using a high-throughput RNA sequencing technology (RNA-Seq) to screen for genes that were related to Mongolian horse testis development and spermatogenesis.Results & Discussion: A total of 16,237 upregulated genes and 8,641 downregulated genes in the testis of Mongolian horse were detected. These genes play important roles in different developmental stages of spermatogenesis and testicular development. Five alternative splicing (AS) event genes were detected, and different AS events can also influence both spermatogenesis and developing of testis. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed for functional annotation of the differentially expressed genes during testis development and spermatogenesis. For example, oocyte meiosis pathways were significantly involved in different stages of testis development and spermatogenesis.Conclusion: These genes were associated with spermatogenesis, male gamete generation, spermatid development, and oocyte meiosis.The finding that gene is a vital element in horse testis development improves our understanding of horse testis development and spermatogenesis.


Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Akisa Nemoto ◽  
Reona Kobayashi ◽  
Sho Yoshimatsu ◽  
Yuta Sato ◽  
Takahiro Kondo ◽  
...  

The common marmoset (Callithrix jacchus) has attracted considerable attention, especially in the biomedical science and neuroscience research fields, because of its potential to recapitulate the complex and multidimensional phenotypes of human diseases, and several neurodegenerative transgenic models have been reported. However, there remain several issues as (i) it takes years to generate late-onset disease models, and (ii) the onset age and severity of phenotypes can vary among individuals due to differences in genetic background. In the present study, we established an efficient and rapid direct neuronal induction method (induced neurons; iNs) from embryonic and adult marmoset fibroblasts to investigate cellular-level phenotypes in the marmoset brain in vitro. We overexpressed reprogramming effectors, i.e., microRNA-9/9*, microRNA-124, and Achaete-Scute family bHLH transcription factor 1, in fibroblasts with a small molecule cocktail that facilitates neuronal induction. The resultant iNs from embryonic and adult marmoset fibroblasts showed neuronal characteristics within two weeks, including neuron-specific gene expression and spontaneous neuronal activity. As directly reprogrammed neurons have been shown to model neurodegenerative disorders, the neuronal reprogramming of marmoset fibroblasts may offer new tools for investigating neurological phenotypes associated with disease progression in non-human primate neurological disease models.


2016 ◽  
Vol 25 (4) ◽  
pp. 943-958 ◽  
Author(s):  
Yun Huang ◽  
Frédéric J. J. Chain ◽  
Mahesh Panchal ◽  
Christophe Eizaguirre ◽  
Martin Kalbe ◽  
...  

2020 ◽  
Author(s):  
Hengyou Zhang ◽  
Zhenbin Hu ◽  
Yuming Yang ◽  
Xiaoqian Liu ◽  
Haiyan Lv ◽  
...  

Abstract Background: Seeds are the economic basis of oilseed crops, especially for soybean, thus far the most widely cultivated oilseed crop worldwide. Seed development is accompanied with a multitude of diverse cellular processes and revealing the underlying regulatory activities is critical for seed improvement. Results: Here, we profiled transcriptomes of developing seeds (20, 25, 30, 40 days after flowering) representing key points of seed development from early to full development. We identified a set of highly-abundant genes and highlighted the importance of these genes to support nutrient accumulation and transcriptional regulation in developing seeds. We identified 8,925 differentially expressed genes that exhibited temporal expression patterns over the course and had expression specificities in distinct tissues including seeds and non-seed tissues (roots, stems, leaves). Genes with specificities to non-seed tissues have tissue-specialized roles while remain relatively low transcript abundance in developing seeds, exhibiting their supportive roles spatially for seed development. Co-expression network analysis identified several under-explored genes in soybean that bridge tissue-specific gene modules. Conclusions: Our study provides a global view of gene activities and biological processes critical for seed formation in soybean and prioritizes a set of genes for further study. The results shed insight into the mechanism controlling seed development and storage reserves.


2021 ◽  
Author(s):  
Z Jafarian ◽  
S Khamse ◽  
H Afshar ◽  
Khorram Khorshid HR ◽  
A Delbari ◽  
...  

Abstract Across the human protein-coding genes, the neuron-specific gene, RASGEF1C, contains the longest (GGC)-repeat, spanning its core promoter and 5′ untranslated region (RASGEF1C-201 ENST00000361132.9). RASGEF1C expression dysregulation occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. Here we sequenced the GGC-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across vertebrates. The 6-repeat allele of this repeat was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (Mid-P exact = 0.004). We also detected divergent genotypes that were present in five NCD patients and not in the controls (Mid-P exact = 0.007). This STR expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. Indication of natural selection for predominantly abundant STR alleles and divergent genotypes enhance the perspective of evolutionary biology and disease pathogenesis in human complex disorders.


2020 ◽  
Vol 8 (1) ◽  
pp. 71-86 ◽  
Author(s):  
Huiran Liu ◽  
Gang Li ◽  
Xiujuan Yang ◽  
Hendrik N.J. Kuijer ◽  
Wanqi Liang ◽  
...  

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Ho Lee ◽  
Kyung Woon Kim ◽  
So Min Lee ◽  
So Young Kim

Abstract Background This study aimed to investigate the changes in the expression of hippocampal genes upon acute noise exposure. Methods Three-week-old Sprague–Dawley rats were assigned to control (n = 15) and noise (n = 15) groups. White noise (2–20 kHz, 115 dB sound pressure level [SPL]) was delivered for 4 h per day for 3 days to the noise group. All rats were sacrificed on the last day of noise exposure, and gene expression in the hippocampus was analyzed using a microarray. Pathway analyses were conducted for genes that showed differential expression ≥ 1.5-fold and P ≤ 0.05 compared to the control group. The genes included in the putative pathways were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results Thirty-eight upregulated genes and 81 downregulated genes were identified. The pathway analyses revealed that upregulated genes were involved in the cellular responses to external stimuli and immune system pathways. qRT-PCR confirmed the upregulation of the involved genes. The downregulated genes were involved in neuronal systems and synapse-related pathways, and qRT-PCR confirmed the downregulation of the involved genes. Conclusions Acute noise exposure upregulated the expression of immune-related genes and downregulated the expression of neurotransmission-related genes in the hippocampus.


Sign in / Sign up

Export Citation Format

Share Document