Project description:Adult neurogenesis in the murine dentate gyrus occurs in a specialized microenvironment that sustains the generation of neurons during life. To fully understand adult neurogenesis, it is essential to determine the neural stem cell (NSC) and progenitor developmental stages, their molecular determinants, and the niche cellular and molecular composition. We report on a single cell RNA sequencing study of the hippocampal niche, performed by isolating all the non-neuronal cell populations. Our analysis provides a comprehensive description of the dentate gyrus cells and allows the identification of exclusive cell type-specific markers. We define the developmental stages and transcriptional dynamics of NSCs and progenitors, and find that while NSCs represent a heterogeneous cellular continuum, progenitors can be grouped in distinct subtypes. We determine the oligodendrocyte lineage and transcriptional dynamics, and describe microglia transcriptional profile and activation state. The combined data constitutes a valuable resource to understand regulatory mechanisms of adult neurogenesis.
Project description:Somatic stem cells contribute to tissue ontogenesis, homeostasis, and regeneration through sequential processes. Systematic molecular analysis of stem cell behavior is challenging because classic approaches cannot resolve cellular heterogeneity or capture developmental dynamics. Here we provide a comprehensive resource of single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny. We further developed Waterfall, a bioinformatic suite, to statistically quantify singe-cell gene expression along de novo reconstructed continuous developmental trajectory. Our study reveals molecular signatures of qNSCs, characterized by high niche signaling integration and low protein translation capacity. Our analyses further delineate molecular cascades underlying adult qNSC activation and neurogenesis initiation, exemplified by decreased extrinsic signaling capacity, primed translational machinery, and regulatory switches in transcription factors, metabolism, and energy sources. Our study reveals the molecular continuum underlying adult neurogenesis and illustrates how Waterfall can be used for single-cell omics analyses of various continuous biological processes. Single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny.
Project description:Epilepsy is a global neurological condition affecting over 70 million people. Therin, temporal lobe epilepsy stands to be the most common type of refractory epilepsy critically featured by hippocampal sclerosis. In this study, single-nucleus RNA-sequencing was performed on the nineteen hippocampus samples of patients with hippocampal sclerosis, presenting the first single-nucleus resolution cellular and molecular landscape of human hippocampal sclerosis.
Project description:Hippocampal organoids are derived from human induced pluripotent stem cells under the guidance of multiple growth factors, such as proteins, chemical inhibitors, and activators. We used single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic signature of hippocampal organoids so that we could characterize cell identities in them. We prepared two single-cell samples from day-70 and day-81 hippocampal organoids.
Project description:To investigate the cell types involved in the gliovascular niche of the zebrafish brain, we performed single cell sequencing on cells sorted from fli1:gfp and her4: GFP transgenic animals in control and amyloid toxicity conditions.
Project description:(Single Cell Sequencing Data) Here we present an integrative, bottom-up approach towards emulating the human bone marrow in vitro. Our method harnesses the regenerative capacity of adult stem cells to self-assemble a complex, specialized microenvironment of human hematopoietic stem cells (HSCs) in a vascularized three-dimensional microphysiological system. Through flow cytometry and single-cell transcriptomic interrogation, we show that the microengineered niche can reconstitute HSC self-renewal, multilineage hematopoiesis, and complex ligand-receptor signaling pathways of the native human marrow. The ability of our model to generate functionally mature myeloid cells also makes it possible to mimic the key physiological processes of innate immunity including neutrophil chemotaxis and intravascular mobilization. To demonstrate the advanced application of the bone marrow-on-a-chip, we present i) a specialized model of bone marrow ablation by proton beam radiotherapy and ii) a multiorgan model of innate immune response against bacterial lung infection. This work advances our ability to reconstruct, probe, and deconvolve the complexity of the bone marrow niche, and may enable new capabilities to model human hematopoiesis and immunity for biomedical and pharmaceutical applications.
Project description:By comparing single cell transcriptomes of neurons participating in medial vs. lateral hippocampal networks in the mouse, we identify Latrophilin-2 as a molecular marker of the lateral network.