Project description:Microglia, the resident immune cells of the brain, have emerged as crucial regulators of synaptic refinement and therefore wiring precision. However, whether the remodeling of distinct synapses during development is mediated by specialized microglia is unknown. Here, using in vivo two-photon imaging, we show that GABA-receptive microglia selectively interact with inhibitory synapses during a critical window of mouse postnatal development. GABA initiates a transcriptional synapse remodeling program within these specialized microglia, which in turn sculpt inhibitory connectivity without impacting excitatory synapses. Ablation of GABAB receptors within microglia impairs this process and leads to stereotyped repetitive behavior and hyperactivity. These findings demonstrate that distinct microglia differentially engage with specific synapse types during development.
Project description:MicroRNAs (miRNAs) act as important epigenetic post-transcriptional regulators of gene expression. We aimed to gain more understanding to the complex gene expression regulation of endometrial receptivity by analysing miRNA signature of fertile human endometrium. We used Agilent miRNA arrays to define the miRNA expression pattern in receptive (LH+7, n = 3) vs. pre-receptive (LH<7, n = 4) endometrium from healthy fertile women.
Project description:How neuronal connections are established and organized in functional networks determines brain function. In the mouse cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made parsing interneuron diversity, yet the molecular mechanisms by which interneuron subtype-specific connectivity motifs emerge remain unclear. Here we investigate transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits. We found that whether the interneurons synapse with pyramidal neurons on their dendrites, soma, or axon initial segment is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.
Project description:The inner uterine lining (endometrium) has been shown to have a distinct methylation pattern that changes throughout the menstrual cycle. However, not much is known about how the endometrial methylome affects endometrial receptivity to implanting embryo in the second half of the menstrual cycle. The aim of the present study was to use genome-wide technologies and a paired study design to characterize the endometrial methylome in pre-receptive and receptive endometrium sampled from 17 healthy women within the same menstrual cycle.
Project description:Neurotransmitters have been well-documented to determine immune cell fates; however, whether and how γ-amino butyric acid (GABA) shapes the function of innate immune cells is still obscure. Here, we demonstrated that GABA orchestrates macrophage maturation and inflammation. GABA treatment during macrophage maturation inhibits interleukin (IL)-1β production from inflammatory macrophages. Mechanistically, GABA enhances succinate-FAD-lysine demethylase1 (LSD1) signaling to regulate the histone demethylation of Bcl2l11 and Dusp2, lowering the formation of NLRP3-ASC-Caspase-1 complex. Meanwhile, GABA-succinate axis lowers succinylation of mitochondrial proteins to promote mitochondrial oxidative phosphorylation (OXPHOS). We also found that GABA alleviates the LPS-induced sepsis as well as high-fat diet-induced obesity in mice. Our study proves that GABA is potential in lessening the pro-inflammatory macrophage responses associating with metabolic reprogramming and protein succinylation, thus providing a strategy for treating macrophage-related inflammatory diseases.
Project description:In the present study, RNA-seq technique was used to compare the expression profiles of circRNAs from goat endometrium samples at gestational day 5 (pre-receptive endometrium, PE) and day 15 (receptive endometrium, RE). A total of 21,813 circRNAs were identified in goat endometrium, of which only 31.22% (6,810) circRNAs were co-expressed at both stages, and 5,925 circRNAs were identified specifically in RE and 9,078 in PE, suggesting high stage specificity in the circRNAs in dairy goats. Further analysis found that there were 334 DECs (differentially expressed circRNAs) in RE compared to PE (P< 0.05), and circRNA8077 was up-regulated with the highest FPKM value in RE. It was noteworthy that half of the up-regulated circRNAs with top 10 highest FPKM value in RE were come from CRIM1. Moreover, GO and KEGG analysis of the hgDEGs (hosting genes of DECs) revealed some circRNAs, genes and pathways that may involve in the formation of the receptive endometrium in dairy goats. In a word, our data provided an endometrium circRNA expression atlas related to the biology of the goat receptive endometrium during embryo implantation, and the results suggested that a subset of circRNAs might involve in the processes of the formation and development of endometrial receptivity.
Project description:NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers an anxiety-like behavior in vivo and induces anxiety-like behavior in a mouse model of chronic social defeat stress.
Project description:The aim of this study was to establish an in vitro model to investigate the initial stages of human implantation based on co-culture of a) immortalized cells representing the receptive (Ishikawa) or non-receptive (HEC-1-A) endometrial epithelium with b) spheroids of a trophoblastic cell line (JEG-3) modified to express green fluorescent protein. After co-culturing Ishikawa cells with trophoblast spheroids, 310 and 298 genes increased or decreased their expression compared to non-co-cultured Ishikawa control cells, respectively; only 9 genes (5 increased and 4 decreased) were differentially expressed in HEC-1-A upon co-culture with trophoblast spheroids. Compared to HEC-1-A, the trophoblast challenge to Ishikawa cells differentially regulated the expression of 495 genes. In summary, upon co-culture with the trophoblast spheroids, non-receptive epithelium is characterized by a muted transcriptional response which in turn fails to activate the full transcriptional response that trophoblast spheroids undergo when co-cultured with receptive epithelium.
Project description:We have previously shown that GABA ainhibits caspase activation and promote axon regeneration in descending neurons of the sea lamprey brainstem after a complete spinal cord injury. Here, we repeated this treatment and performed Illumina RNA sequencing studies in the brainstems of control and GABA treated animals.