eQTLs play critical roles in regulating gene expression and identifying key regulators in rice.

The regulation of gene expression plays an essential role in both the phenotype and adaptation of plants. Transcriptome sequencing enables simultaneous identification of exonic variants and quantification of gene expression. Here, we sequenced the leaf transcriptomes of 287 rice accessions from around the world and obtained a total of 177 853 high-quality single nucleotide polymorphisms after filtering. Genome-wide association study identified 44 354 expression quantitative trait loci (eQTLs), which regulate the expression of 13 201 genes, as well as 17 local eQTL hotspots and 96 distant eQTL hotspots. Furthermore, a transcriptome-wide association study screened 21 candidate genes for starch content in the flag leaves at the heading stage. HS002 was identified as a significant distant eQTL hotspot with five downstream genes enriched for diterpene antitoxin synthesis. Co-expression analysis, eQTL analysis, and linkage mapping together demonstrated that bHLH026 acts as a key regulator to activate the expression of downstream genes. The transgenic assay revealed that bHLH026 is an important regulator of diterpenoid antitoxin synthesis and enhances the disease resistance of rice. These findings improve our knowledge of the regulatory mechanisms of gene expression variation and complex regulatory networks of the rice genome and will facilitate genetic improvement of cultivated rice varieties.

Systems-level analysis identifies key regulators driving epileptogenesis in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most prevalent and often devastating form of epilepsy. The molecular mechanism underlying the development of TLE remains largely unclear, which hinders the discovery of effective antiepileptogenic drugs. Here we adopted a systems-level approach integrating transcriptomic profiles of three epileptogenesis stages to identify key regulators underlying epilepsy progression. Associating stage-specific gene meta-signatures with brain cell-specialized modules revealed positive regulation of glial migration and adhesion, cytokine production, and neuron death, and downregulation of synaptic transmission and ion transport during epileptogenesis. We identified 265 key regulators driving these processes and 72 of them were demonstrated associating with seizure frequency and/or hippocampal sclerosis in human TLE. Importantly, the upregulation of FAM107A, LAMB2, LTBP1 and TGIF1, which are mainly involved in nervous system development, were found contributing to both conditions. Our findings present the evolution landscape of epileptogenesis and provide candidate regulators that may serve as potential antiepileptogenic targets.

Integrated Omics Analysis Reveals Key Pathways in Cotton Defense against Mirid Bug (Adelphocoris suturalis Jakovlev) Feeding.

The recent dominance of Adelphocoris suturalis Jakovlev as the primary cotton field pest in Bt-cotton-cultivated areas has generated significant interest in cotton pest control research. This study addresses the limited understanding of cotton defense mechanisms triggered by A. suturalis feeding. Utilizing LC-QTOF-MS, we analyzed cotton metabolomic changes induced by A. suturalis, and identified 496 differential positive ions (374 upregulated, 122 downregulated) across 11 categories, such as terpenoids, alkaloids, phenylpropanoids, flavonoids, isoflavones, etc. Subsequent iTRAQ-LC-MS/MS analysis of the cotton proteome revealed 1569 differential proteins enriched in 35 metabolic pathways. Integrated metabolome and proteome analysis highlighted significant upregulation of 17 (89%) proteases in the α-linolenic acid (ALA) metabolism pathway, concomitant with a significant increase in 14 (88%) associated metabolites. Conversely, 19 (73%) proteases in the fructose and mannose biosynthesis pathway were downregulated, with 7 (27%) upregulated proteases corresponding to the downregulation of 8 pathway-associated metabolites. Expression analysis of key regulators in the ALA pathway, including allene oxidase synthase (AOS), phospholipase A (PLA), allene oxidative cyclase (AOC), and 12-oxophytodienoate reductase3 (OPR3), demonstrated significant responses to A. suturalis feeding. Finally, this study pioneers the exploration of molecular mechanisms in the plant-insect relationship, thereby offering insights into potential novel control strategies against this cotton pest.

Comparative transcriptome and proteome analysis explores the antitumor key regulators of ergosterone in H22 tumor-bearing mice.

Ergosterone has been proved to have potential antitumor effect on H22 tumor-bearing mice, but the antitumor mechanism and key regulators are still unclear. The current study was aimed to explore the key regulators responsible for antitumor of ergosterone using whole transcriptome and proteome analysis in H22 tumor-bearing mice model. The model of H22 tumor-bearing mice was constructed according to the histopathological data and biochemical parameters. The isolated tumor tissues of different treatment groups were subjected to transcriptomic and proteomic analysis. Our findings demonstrated that 472 differentially expressed genes and 658 proteins were identified in the tumor tissue of different treatment groups through RNA-Seq and liquid chromatography with tandem mass spectrometry-based proteomic analysis, respectively. The combined omics analysis revealed three critical genes/proteins, including Lars2, Sirpα and Hcls1 that could play a role in antitumor pathways. Furthermore, Lars2, Sirpα and Hcls1 genes/proteins, as key regulators of the antitumor effect of ergosterone, were verified by qRT-PCR and western blotting methods, respectively. In summary, our study provides new insights into analysing the antitumor mechanism of ergosterone from the point of view of gene and protein expression and will encourage further development of the antitumor pharmaceutical industry.

Molecular differences in brain regional vulnerability to aging between males and females.

Background: Aging-related cognitive decline is associated with brain structural changes and synaptic loss. However, the molecular mechanisms of cognitive decline during normal aging remain elusive. Results: Using the GTEx transcriptomic data from 13 brain regions, we identified aging-associated molecular alterations and cell-type compositions in males and females. We further constructed gene co-expression networks and identified aging-associated modules and key regulators shared by both sexes or specific to males or females. A few brain regions such as the hippocampus and the hypothalamus show specific vulnerability in males, while the cerebellar hemisphere and the anterior cingulate cortex regions manifest greater vulnerability in females than in males. Immune response genes are positively correlated with age, whereas those involved in neurogenesis are negatively correlated with age. Aging-associated genes identified in the hippocampus and the frontal cortex are significantly enriched for gene signatures implicated in Alzheimer's disease (AD) pathogenesis. In the hippocampus, a male-specific co-expression module is driven by key synaptic signaling regulators including VSNL1, INA, CHN1 and KCNH1; while in the cortex, a female-specific module is associated with neuron projection morphogenesis, which is driven by key regulators including SRPK2, REPS2 and FXYD1. In the cerebellar hemisphere, a myelination-associated module shared by males and females is driven by key regulators such as MOG, ENPP2, MYRF, ANLN, MAG and PLP1, which have been implicated in the development of AD and other neurodegenerative diseases. Conclusions: This integrative network biology study systematically identifies molecular signatures and networks underlying brain regional vulnerability to aging in males and females. The findings pave the way for understanding the molecular mechanisms of gender differences in developing neurodegenerative diseases such as AD.

Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury.

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.

The Genetic and Hormonal Inducers of Continuous Flowering in Orchids: An Emerging View.

Orchids are the flowers of magnetic beauty. Vivid and attractive flowers with magnificent shapes make them the king of the floriculture industry. However, the long-awaited flowering is a drawback to their market success, and therefore, flowering time regulation is the key to studies about orchid flower development. Although there are some rare orchids with a continuous flowering pattern, the molecular regulatory mechanisms are yet to be elucidated to find applicable solutions to other orchid species. Multiple regulatory pathways, such as photoperiod, vernalization, circadian clock, temperature and hormonal pathways are thought to signalize flower timing using a group of floral integrators. This mini review, thus, organizes the current knowledge of floral time regulators to suggest future perspectives on the continuous flowering mechanism that may help to plan functional studies to induce flowering revolution in precious orchid species.

Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach.

Spina Bifida (SB) is a congenital spinal cord malformation. Efforts to discern the key regulators (KRs) of the SB protein-protein interaction (PPI) network are requisite for developing its successful interventions. The architecture of the SB network, constructed from 117 manually curated genes was found to self-organize into a scale-free fractal state having a weak hierarchical organization. We identified three modules/motifs consisting of ten KRs, namely, TNIP1, TNF, TRAF1, TNRC6B, KMT2C, KMT2D, NCOA3, TRDMT1, DICER1, and HDAC1. These KRs serve as the backbone of the network, they propagate signals through the different hierarchical levels of the network to conserve the network's stability while maintaining low popularity in the network. We also observed that the SB network exhibits a rich-club organization, the formation of which is attributed to our key regulators also except for TNIP1 and TRDMT1. The KRs that were found to ally with each other and emerge in the same motif, open up a new dimension of research of studying these KRs together. Owing to the multiple etiology and mechanisms of SB, a combination of several biomarkers is expected to have higher diagnostic accuracy for SB as compared to using a single biomarker. So, if all the KRs present in a single module/motif are targetted together, they can serve as biomarkers for the diagnosis of SB. Our study puts forward some novel SB-related genes that need further experimental validation to be considered as reliable future biomarkers and therapeutic targets.

Conserved versatile master regulators in signalling pathways in response to stress in plants.

From the first land plants to the complex gymnosperms and angiosperms of today, environmental conditions have forced plants to develop molecular strategies to surpass natural obstacles to growth and proliferation, and these genetic gains have been transmitted to the following generations. In this long natural process, novel and elaborate mechanisms have evolved to enable plants to cope with environmental limitations. Elements in many signalling cascades enable plants to sense different, multiple and simultaneous ambient cues. A group of versatile master regulators of gene expression control plant responses to stressing conditions. For crop breeding purposes, the task is to determine how to activate these key regulators to enable accurate and optimal reactions to common stresses. In this review, we discuss how plants sense biotic and abiotic stresses, how and which master regulators are implied in the responses to these stresses, their evolution in the life kingdoms, and the domains in these proteins that interact with other factors to lead to a proper and efficient plant response.