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Gou, B.

Publications and source records attributed to Gou, B..

5 recordsLinked to original sources

A retinal adrenergic module tunes mammalian visual evolution

How conserved neural circuits are modified during mammalian evolution remains poorly understood. Here we combine cross-species single-cell transcriptomics, in situ validation, retinal physiology, and conditional genetics to identify a superorder-associated adrenergic module in the mammalian retina. We find that ADRB1, which encodes the {beta}1-adrenergic receptor, is uniquely expressed in rod bipolar cells of sampled Euarchontoglires, but is absent from homologous cells in sampled Laurasiatheria and Marsupialia. In mice, {beta}1-adrenergic receptor localizes to rod bipolar cell terminals and boosts transmission to AII amacrine cells through Gs-adenylyl cyclase-cAMP-PKA signaling pathway. This modulation enhances synchronous release, accelerates downstream ganglion cell output, and increases scotopic electroretinographic responses, while rod-bipolar-cell-specific Adrb1 deletion abolishes norepinephrine-induced enhancement without disrupting baseline vision. In the diurnal tree shrew, a Euarchontoglires species with a cone-dominated retina, ADRB1 is instead redeployed from rod bipolar cells to cone photoreceptors. These findings reveal an evolutionarily mobile neuromodulatory module that tunes retinal computation according to visual ecology.

evolutionary biology↗

NLR from soybean Rsv1 locus confers broad-spectrum resistance to soybean mosaic virus G1-G7 strains by recognizing viral P3 protein

Nucleotide-binding leucine-rich repeat (NLR) immune receptor genes are of significant value in disease resistance breeding and the control of viral diseases. Soybean mosaic virus (SMV) poses a serious threat to soybean production and the Rsv1 locus in soybean cultivar Suweon 97 confers broad-spectrum resistance against SMV strains G1 to G7; however, this locus harbors no fewer than 18 NLR genes, and thus the broad-spectrum antiviral mechanisms underlying the Rsv1 locus remain poorly understood to date. Here, we established a rapid and highly efficient screening system for cloning NLR genes from soybean Rsv1 locus and identified a broad-spectrum antiviral NLR gene 13g184900 from this highly complicated locus. The NLR encoded by 13g184900 can recognize viral P3 protein from all SMV strains (G1-G7) and another potyvirus Bean common mosaic virus (BCMV). The coiled-coil (CC) domain of this NLR directly interacts with viral P3 protein. Additionally, we showed that this NLR originated from wild soybean accession in East China and has been introduced into several soybean cultivars during domestication. Collectively, we developed a high-throughput screening system for identifying NLR genes in soybean and our study provides new mechanistic perspective on how the Rsv1 locus mediates the broad-spectrum resistance to all SMV G1-G7 strains.

plant biology↗

Embryo spatial 3D genomics

The 3D architecture of the genome is crucial for controlling gene expression and organ development. Here, we introduce a spatial 3D genomics approach for assessing chromatin conformation in-situ in tissue sections, by integrating microfluidic deterministic barcoding and SPRITE procedures. This method was applied to mouse embryo sections, revealing a hierarchical model of chromatin interactions within and between compartments in various organs. The intra-compartment interactions vary among organs to orchestrate gene expressions, while the inter-compartment interactions remain identical in the most organs. Beyond this, the liver exhibits overwhelmingly packed chromatin with enhanced adjacent-compartment interactions, possibly related to its physiology. These findings highlight the importance of tissue-spatial information in understanding embryonic chromatin organization. The approach presents a powerful tool for investigating these processes in tissues with high heterogeneity. One Sentence SummaryA spatial 3D genomics approach was developed that accesses hierarchical chromatin conformation in-situ in tissue sections.

genetics↗

Directed robust generation of functional retinal ganglion cells from Muller glia

Glaucoma and optic neuropathies cause progressive and irreversible degeneration of retinal ganglion cells (RGCs) and the optic nerve and are currently without any effective treatment. Previous research into cell replacement therapy of these neurodegenerative diseases has been stalled due to the limited capability for grafted RGCs to integrate into the retina and project properly along the long visual pathway to reach their brain targets. In vivo RGC regeneration would be a promising alternative approach but mammalian retinas lack regenerative capacity even though cold-blood vertebrates such as zebrafish have the full capacity to regenerate a damaged retina using Muller glia (MG) as retinal stem cells. Nevertheless, mammalian MG undergo limited neurogenesis when stimulated by retinal injury. Therefore, a fundamental question that remains to be answered is whether MG can be induced to efficiently regenerate functional RGCs for vision restoration in mammals. Here we show that without stimulating proliferation, the transcription factor (TF) Math5 together with a Brn3 TF family member are able to reprogram mature mouse MG into RGCs with exceedingly high efficiency while either alone has no or limited capacity. The reprogrammed RGCs extend long axons that make appropriate intra-retinal and extra-retinal projections through the entire visual pathway including the optic nerve, optic chiasm and optic tract to innervate both image-forming and non-image-forming brain targets. They exhibit typical neuronal electrophysiological properties and improve visual responses in two glaucoma mouse models: Brn3b null mutant mice and mice with the optic nerve crushed (ONC). Together, our data provide evidence that mammalian MG can be reprogrammed by defined TFs to achieve robust in vivo regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies.

neuroscience↗

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Icariin, the main active ingredient of Epimedium, has played an important role in bone anabolism. However, the molecular mechanism for this effect was not convincingly reported yet. In this paper, the role of icariin on cell morphology, viability, cell cycling and the activity of alkaline phosphatase (ALP) were studied, and the molecular mechanism of icariin induced osteogenic effect was also investigated. Icariin with different concentrations (10, 20 and 40 ng/ml) was used to modify the pre-osteoblastic MC3T3-E1 cells for 48, 72 and 96 h, and the proliferation, morphology, and the cell cycle of the cells were evaluated by Cell Counting Kit-8 (CCK-8), microscopy and flow cytometry, respectively. Bone morphogenic protein-2 (BMP-2), bone morphogenic protein receptor-2 (BMPR-2), Smad4, Smadl/5/8 proteins expression levels were obtained by Western blotting and the expression levels of runt-related transcription factor 2 (Runx2) mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR). In this study, we found that icariin could promote the proliferation and differentiation of MC3T3-E1 cells in a dose - and time-dependent manner. Icariin could stimulate the expression of the BMP-2, BMPR-2, Smad4 and Smadl/5/8 proteins. Furthermore, icariin could upregulate the expression of Runx2 mRNA. These results showed that icariin played an important role in upregulating BMP-2 expression to activate the BMP-2/Smads/Runx2 signal pathway for increasing both the proliferation and differentiation of the MC3T3-E1 cells. However, the osteogenic effects of icariin can be suppressed by the BMP-2 antagonist (Noggin). In conclusion, we demonstrate that icariin is an osteoinductive factor that exerts its osteogenic effect by regulating the BMP-2/Smads/Runx2 signal pathway in MC3T3-E1 cells.

cell biology↗