Journal of Genetics and Genomics最新文献

Nanopore direct RNA sequencing (DRS) provides the direct access to native RNA strands with full-length information, shedding light on rich qualitative and quantitative properties of gene expression profiles. Here with NanoTrans, we present an integrated computational framework that comprehensively covers all major DRS-based application scopes, including isoform clustering and quantification, poly(A) tail length estimation, RNA modification profiling, and fusion gene detection. In addition to its merit in providing such a streamlined one-stop solution, NanoTrans also shines in its workflow-orientated modular design, batch processing capability, all-in-one tabular and graphic report output, as well as automatic installation and configuration supports. Finally, by applying NanoTrans to real DRS datasets of yeast, Arabidopsis, as well as human embryonic kidney and cancer cell lines, we further demonstrate its utility, effectiveness, and efficacy across a wide range of DRS-based application settings.

More and more studies have demonstrated that pseudogenes possess coding ability, and the functions of their transcripts in the development of diseases have been partially revealed. However, the role of pseudogenes in maintenance of normal physiological states and life activities has long been neglected. Here, we identify pseudogenes that are dynamically expressed during human early embryogenesis, showing different expression patterns from that of adult tissues. We explore the expression correlation between pseudogenes and the parent genes, partly due to their shared gene regulatory elements or the potential regulation network between them. The essential role of three pseudogenes, PI4KAP1, TMED10P1, and FBXW4P1, in maintaining self-renewal of human embryonic stem cells is demonstrated. We further find that the three pseudogenes might perform their regulatory functions by binding to proteins or microRNAs. The pseudogene-related single-nucleotide polymorphisms are significantly associated with human congenital disease, further illustrating their importance during early embryonic development. Overall, this study is an excavation and exploration of functional pseudogenes during early human embryonic development, suggesting that pseudogenes are not only capable of being specifically activated in pathological states, but also play crucial roles in the maintenance of normal physiological states.

Netrin-G2 is a membrane-anchored protein known to play critical roles in neuronal circuit development and synaptic organization. In this study, we identify compound heterozygous mutations of c.547delC, p.(Arg183Alafs∗186) and c.605G>A, p.(Trp202X) in NTNG2 causing a syndrome exhibiting developmental delay, intellectual disability, hypotonia, and facial dysmorphism. To elucidate the underlying cellular and molecular mechanisms, CRISPR-Cas9 technology is employed to generate a knock-in mouse model expressing the R183Afs and W202X mutations. We report that the Ntng2^{R183Afs/W202X} mice exhibit hypotonia and impaired learning and memory. We find that the levels of CaMKII and p-GluA1^Ser831 are decreased, and excitatory postsynaptic transmission and long-term potentiation are impaired. To increase the activity of CaMKII, the mutant mice receive intraperitoneal injections of DCP-LA, a CaMKII agonist, and show improved cognitive function. Together, our findings reveal molecular mechanisms of how NTNG2 deficiency leads to impairments of cognitive ability and synaptic plasticity.

Stomata play critical roles in gas exchange and immunity to pathogens. While many genes regulating early stomatal development up to the production of young guard cells (GCs) have been identified in Arabidopsis, much less is known about how young GCs develop into mature functional stomata. Here we perform a maturomics study on stomata, with "maturomics" defined as omics analysis of the maturation process of a tissue or organ. We develop an integrative scheme to analyze three public stomata-related single-cell RNA-seq datasets and identify a list of 586 genes that are specifically up-regulated in all three datasets during stomatal maturation and function formation. The list, termed sc_586, is enriched with known regulators of stomatal maturation and functions. To validate the reliability of the dataset, we selected two candidate G2-like transcription factor genes, MYS1 and MYS2, to investigate their roles in stomata. These two genes redundantly regulate the size and hoop rigidity of mature GCs, and the mys1 mys2 double mutants cause mature GCs with severe defects in regulating their stomatal apertures. Taken together, our results provide a valuable list of genes for studying GC maturation and function formation.

Avian ovaries develop asymmetrically apart from prey birds, with only the left ovary growing more towards functional organ. Here, we analyze over 135,000 cells from chick's left and right ovaries at six distinct embryonic developmental stages utilizing single-cell transcriptome sequencing. We delineate gene expression patterns across 15 cell types within these embryo ovaries, revealing side-specific development. The left ovaries exhibit cortex cells, zygotene germ cells, and transcriptional changes unique to the left side. Differential gene expression analysis further identifies specific markers and pathways active in these cell types, highlighting the asymmetry in ovarian development. A fine-scale analysis of the germ cell meiotic transcriptome reveals seven distinct clusters with gene expression patterns specific to various meiotic stages. The study also identifies signaling pathways and intercellular communications, particularly between pre-granulosa and germ cells. Spatial transcriptome analysis shows the asymmetry, demonstrating cortex cells exclusively in the left ovary, modulating neighboring cell types through putative secreted signaling molecules. Overall, this single-cell analysis provides insights into the molecular mechanisms of the asymmetric development of avian ovaries, particularly the significant role of cortex cells in the left ovary.

Nicotine is widely recognized as the primary contributor to tobacco dependence. Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area (VTA) neurons, and accumulating evidence suggests that glia play prominent roles in nicotine addiction. However, VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration. Here, a male mouse model of nicotine self-administration is established and the timing of three critical phases (pre-addiction, addicting, and post-addiction phase) is characterized. Single-nucleus RNA sequencing in the VTA at each phase is performed to comprehensively classify specific cell subtypes. Adaptive changes occurred during the addicting and post-addiction phases, with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacts the transcription in each cell subtype. Furthermore, significant transcriptional changes in energy metabolism-related genes are observed, accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration. The results provide insights into mechanisms underlying the progression of nicotine addiction, serving as an important resource for identifying potential molecular targets for nicotine cessation.