The Experts below are selected from a list of 32370 Experts worldwide ranked by ideXlab platform
Dominic Grun - One of the best experts on this subject based on the ideXlab platform.
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single cell rna sequencing identifies the Developmental Trajectory of c myc dependent nk1 1 t bet intraepithelial lymphocyte precursors
Mucosal Immunology, 2020Co-Authors: Jonas F Hummel, Patrice Zeis, Karolina Ebert, Jonas Fixemer, Philip Konrad, Christian Schachtrup, Sebastian J Arnold, Dominic GrunAbstract:Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 and CD8 T cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4-CD8αβ-TCRαβ+NK1.1- IEL precursors (NK1.1- IELPs), we define a Developmental Trajectory that can be tracked based on the sequential expression of CD122 and T-bet. Moreover, we identify the Id proteins Id2 and Id3 as a novel regulator of IELP development and show that all NK1.1- IELPs progress through a PD-1 stage that precedes the induction of T-bet. The transition from PD-1 to T-bet is regulated by the transcription factor C-Myc, which has far reaching effects on cell cycle, energy metabolism, and the translational machinery during IELP development. In summary, our results provide a high-resolution molecular framework for thymic IEL development of NK1.1- IELPs and deepen our understanding of this still elusive cell type.
Kelly Perlman - One of the best experts on this subject based on the ideXlab platform.
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Developmental Trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell rna sequencing
Glia, 2020Co-Authors: Kelly Perlman, Charles P Couturier, Moein Yaqubi, Arnaud Tanti, Qiaoling Cui, Florian Pernin, Jo Anne Stratton, Jiannis Ragoussis, Luke M HealyAbstract:Characterizing the Developmental Trajectory of oligodendrocyte progenitor cells (OPC) is of great interest given the importance of these cells in the remyelination process. However, studies of human OPC development remain limited by the availability of whole cell samples and material that encompasses a wide age range, including time of peak myelination. In this study, we apply single cell RNA sequencing to viable whole cells across the age span and link transcriptomic signatures of oligodendrocyte-lineage cells with stage-specific functional properties. Cells were isolated from surgical tissue samples of second-trimester fetal, 2-year-old pediatric, 13-year-old adolescent, and adult donors by mechanical and enzymatic digestion, followed by percoll gradient centrifugation. Gene expression was analyzed using droplet-based RNA sequencing (10X Chromium). Louvain clustering analysis identified three distinct cellular subpopulations based on 5,613 genes, comprised of an early OPC (e-OPC) group, a late OPC group (l-OPC), and a mature OL (MOL) group. Gene ontology terms enriched for e-OPCs included cell cycle and development, for l-OPCs included extracellular matrix and cell adhesion, and for MOLs included myelination and cytoskeleton. The e-OPCs were mostly confined to the premyelinating fetal group, and the l-OPCs were most highly represented in the pediatric age group, corresponding to the peak age of myelination. Cells expressing a signature characteristic of l-OPCs were identified in the adult brain in situ using RNAScope. These findings highlight the transcriptomic variability in OL-lineage cells before, during, and after peak myelination and contribute to identifying novel pathways required to achieve remyelination.
Luke M Healy - One of the best experts on this subject based on the ideXlab platform.
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Developmental Trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell rna sequencing
Glia, 2020Co-Authors: Kelly Perlman, Charles P Couturier, Moein Yaqubi, Arnaud Tanti, Qiaoling Cui, Florian Pernin, Jo Anne Stratton, Jiannis Ragoussis, Luke M HealyAbstract:Characterizing the Developmental Trajectory of oligodendrocyte progenitor cells (OPC) is of great interest given the importance of these cells in the remyelination process. However, studies of human OPC development remain limited by the availability of whole cell samples and material that encompasses a wide age range, including time of peak myelination. In this study, we apply single cell RNA sequencing to viable whole cells across the age span and link transcriptomic signatures of oligodendrocyte-lineage cells with stage-specific functional properties. Cells were isolated from surgical tissue samples of second-trimester fetal, 2-year-old pediatric, 13-year-old adolescent, and adult donors by mechanical and enzymatic digestion, followed by percoll gradient centrifugation. Gene expression was analyzed using droplet-based RNA sequencing (10X Chromium). Louvain clustering analysis identified three distinct cellular subpopulations based on 5,613 genes, comprised of an early OPC (e-OPC) group, a late OPC group (l-OPC), and a mature OL (MOL) group. Gene ontology terms enriched for e-OPCs included cell cycle and development, for l-OPCs included extracellular matrix and cell adhesion, and for MOLs included myelination and cytoskeleton. The e-OPCs were mostly confined to the premyelinating fetal group, and the l-OPCs were most highly represented in the pediatric age group, corresponding to the peak age of myelination. Cells expressing a signature characteristic of l-OPCs were identified in the adult brain in situ using RNAScope. These findings highlight the transcriptomic variability in OL-lineage cells before, during, and after peak myelination and contribute to identifying novel pathways required to achieve remyelination.
Patrice Zeis - One of the best experts on this subject based on the ideXlab platform.
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single cell rna sequencing identifies the Developmental Trajectory of c myc dependent nk1 1 t bet intraepithelial lymphocyte precursors
Mucosal Immunology, 2020Co-Authors: Jonas F Hummel, Patrice Zeis, Karolina Ebert, Jonas Fixemer, Philip Konrad, Christian Schachtrup, Sebastian J Arnold, Dominic GrunAbstract:Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 and CD8 T cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4-CD8αβ-TCRαβ+NK1.1- IEL precursors (NK1.1- IELPs), we define a Developmental Trajectory that can be tracked based on the sequential expression of CD122 and T-bet. Moreover, we identify the Id proteins Id2 and Id3 as a novel regulator of IELP development and show that all NK1.1- IELPs progress through a PD-1 stage that precedes the induction of T-bet. The transition from PD-1 to T-bet is regulated by the transcription factor C-Myc, which has far reaching effects on cell cycle, energy metabolism, and the translational machinery during IELP development. In summary, our results provide a high-resolution molecular framework for thymic IEL development of NK1.1- IELPs and deepen our understanding of this still elusive cell type.
Jocelyne Bachevalier - One of the best experts on this subject based on the ideXlab platform.
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rhesus macaque brain Developmental Trajectory a longitudinal analysis using tensor based structural morphometry and diffusion tensor imaging
Cerebral Cortex, 2020Co-Authors: Jeongchul Kim, Youngkyoo Jung, Richard Barcus, Jocelyne Bachevalier, Mar M Sanchez, Michael A Nader, Christopher T WhitlowAbstract:The typical Developmental Trajectory of brain structure among nonhuman primates (NHPs) remains poorly understood. In this study, we characterized the normative Trajectory of Developmental change among a cohort of rhesus monkeys (n = 28), ranging in age from 2 to 22 months, using structural MRI datasets that were longitudinally acquired every 3-4 months. We hypothesized that NHP-specific transient intracranial volume decreases reported during late infancy would be part of the typical Developmental process, which is driven by volumetric contraction of gray matter in primary functional areas. To this end, we performed multiscale analyses from the whole brain to voxel level, characterizing regional heterogeneity, hemispheric asymmetry, and sexual dimorphism in Developmental patterns. The longitudinal Trajectory of brain development was explained by three different regional volumetric growth patterns (exponentially decreasing, undulating, and linearly increasing), which resulted in Developmental brain volume curves with transient brain volumetric decreases. White matter (WM) fractional anisotropy increased with age, corresponding to WM volume increases, while mean diffusivity (MD) showed biphasic patterns. The longitudinal Trajectory of brain development in young rhesus monkeys follows typical maturation patterns seen in humans, but regional volumetric and MD changes are more dynamic in rhesus monkeys compared with humans, with marked decreases followed by "rebound-like" increases.
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Developmental Trajectory of Object Recognition Memory in Infant Rhesus Macaques with and without Neonatal Hippocampal Lesions
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010Co-Authors: Alyson Zeamer, Eric Heuer, Jocelyne BachevalierAbstract:To examine the Developmental Trajectory of object recognition memory and its neural substrate, 10–12-d-old monkeys ( Macaca mulatta ) received sham operations or neurotoxic hippocampal lesions and were tested at the ages of 1.5, 6, and 18 months on the visual paired-comparison task using delays of 10, 30, 60, and 120 s. In sham-operated controls, incidental recognition memory was present at 1.5 months, became more robust at 6 months, and was delay-dependent by 18 months of age, suggesting that the brain structures mediating these early developing recognition abilities may undergo significant modifications after 6 months of age in monkeys. A similar Developmental progression was also observed in animals with neonatal hippocampal lesions, although the delay-dependent effect at 18 months was significantly more pronounced after the neonatal hippocampal lesions, suggesting that with maturation animals with neonatal hippocampal lesions grow into a recognition-memory deficit. These findings suggest not only that the medial temporal cortical areas, known to mediate incidental recognition memory processes in adulthood, could support these processes in early infancy even when long delays are used, but also that later in development, after reaching functional maturity, the hippocampus begins to interact with the medial temporal cortical areas to mediate this function.