scholarly journals Single Cell Transcriptional Profiling of Phox2b-Expressing Geniculate Ganglion Neurons

2019 ◽  
Author(s):  
Catherine B. Anderson ◽  
Eric D. Larson
Keyword(s):  
Single Cell ◽  
Cell Activation ◽  
Transcriptional Profiling ◽  
Taste Receptor ◽  
Nerve Fibers ◽  
The Body ◽  
Molecular Heterogeneity ◽  
Geniculate Ganglion ◽  
Gustatory Nerve ◽  
Ganglion Neurons

AbstractThe sense of taste is fundamental for survival as harmful substances can be discriminated and prevented from entering the body. Taste buds act as chemosensory sentinels and detect bitter, salty, sweet, sour, and umami substances and transmit signals to afferent nerve fibers. Whether a single gustatory nerve fiber selectively is responsive to a single taste modality (through taste receptor cell activation) is a point of contention in the field.. In the present study, we present a method for single cell RNA sequencing of gustatory geniculate ganglion neurons and compare the results obtained to two prior published works. Additionally, independent reanalysis of the raw data from these previous studies confirms molecular heterogeneity of ganglion neurons. Multiple gustatory clusters are found, and we compare cluster markers identified by the original works and those identified in the present study. Across all datasets and analyses, specific clusters show a high degree of correlation including a somatosensory cluster (Phox2b-, Piezo2+, Fxyd2+), a potential sweet-best cluster (Phox2b+, Spon1+, Olfm3+), and a potential sour-best cluster (Phox2b+, Penk+, Htr3a+). Additionally, a putative mechanosensitive gustatory cluster with an unknown functional role is identified (Phox2b+, Piezo2+, Calb1+). Other gustatory clusters (Phox2b+) are more varied across analyses, but are marked by Olfm3. Which, if any, clusters comprise umami-best, bitter-best, or salty-best fibers will require further study.

scholarly journals Single-cell transcriptomic analysis of the adult mouse spinal cord

2020 ◽  
Author(s):  
Jacob A. Blum ◽  
Sandy Klemm ◽  
Lisa Nakayama ◽  
Arwa Kathiria ◽  
Kevin A. Guttenplan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Single Cell ◽  
Motor Neurons ◽  
The Body ◽  
Molecular Heterogeneity ◽  
Spinal Motor Neuron ◽  
Spinal Motor ◽  
Full Complement ◽  
Adult Spinal Cord

AbstractThe spinal cord is a fascinating structure responsible for coordinating all movement in vertebrates. Spinal motor neurons control the activity of virtually every organ and muscle throughout the body by transmitting signals that originate in the spinal cord. These neurons are remarkably heterogeneous in their activity and innervation targets. However, because motor neurons represent only a small fraction of cells within the spinal cord and are difficult to isolate, the full complement of motor neuron subtypes remains unknown. Here we comprehensively describe the molecular heterogeneity of motor neurons within the adult spinal cord. We profiled 43,890 single-nucleus transcriptomes using fluorescence-activated nuclei sorting to enrich for spinal motor neuron nuclei. These data reveal a transcriptional map of the adult mammalian spinal cord and the first unbiased characterization of all transcriptionally distinct autonomic and somatic spinal motor neuron subpopulations. We identify 16 sympathetic motor neuron subtypes that segregate spatially along the spinal cord. Many of these subtypes selectively express specific hormones and receptors, suggesting neuromodulatory signaling within the autonomic nervous system. We describe skeletal motor neuron heterogeneity in the adult spinal cord, revealing numerous novel markers that distinguish alpha and gamma motor neurons—cell populations that are specifically affected in neurodegenerative disease. We also provide evidence for a novel transcriptional subpopulation of skeletal motor neurons. Collectively, these data provide a single-cell transcriptional atlas for investigating motor neuron diversity as well as the cellular and molecular basis of motor neuron function in health and disease.

scholarly journals Transcriptional program of memory B cell activation, broadly binding anti-influenza antibodies, and bystander activation after vaccination revealed by single-cell transcriptomics

2019 ◽  
Author(s):  
Felix Horns ◽  
Cornelia L. Dekker ◽  
Stephen R. Quake
Keyword(s):  
Influenza Vaccination ◽  
B Cell ◽  
Single Cell ◽  
Cell Activation ◽  
Transcriptional Profiling ◽  
Affinity Maturation ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Memory B Cell ◽  
Clonal Proliferation

AbstractAntibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profiled the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements. Single-cell transcriptional profiling revealed a program of memory B cell activation characterized by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function. Vaccination elicited an antibody clone which rapidly acquired broad high-affinity hemagglutinin binding during affinity maturation. Unexpectedly, many antibody clones elicited by vaccination do not bind vaccine, demonstrating non-specific activation of bystander antibodies by influenza vaccination. These results offer insight into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall.

scholarly journals Single-Cell Transcriptional Profiling of the Adult Corticospinal Tract Reveals Forelimb and Hindlimb Molecular Specialization

2021 ◽  
Author(s):  
Noa Golan ◽  
Sierra Dawn Kauer ◽  
Daniel Benjamin Ehrlich ◽  
Neal Ravindra ◽  
David van Dijk ◽  
...  
Keyword(s):  
Single Cell ◽  
Corticospinal Tract ◽  
Transcriptional Profiling ◽  
Axon Growth ◽  
Retrograde Tracing ◽  
Motor Deficits ◽  
Molecular Heterogeneity ◽  
Cord Injury ◽  
Cns Trauma ◽  
Insight Into

The corticospinal tract (CST) is refractory to repair after CNS trauma, resulting in chronic debilitating functional motor deficits after spinal cord injury. While novel pro-axon growth activators have stimulated plasticity and regeneration of corticospinal neurons (CSNs) after injury, robust functional recovery remains elusive. These repair strategies are sub-optimal in part due to underexplored molecular heterogeneity within the developing and adult CST. In this study, we combine retrograde CST tracing with single-cell RNA sequencing to build a comprehensive atlas of CSN subtypes. By comparing CSNs to non-spinally projecting neurons in layer Vb, we identify pan-CSN markers including Wnt7b. By leveraging retrograde tracing, we are able to compare forelimb and hindlimb projecting CSNs, identifying subtype-specific markers, including Cacng7 and Slc16a2 respectively. These markers are expressed in embryonic and neonatal CSNs and can be used to study early postnatal patterning of the CST. Our results provide molecular insight into the differences between anatomically distinct CSN subtypes and provide a resource for future screening and exploitation of these subtypes to repair the damaged CST after injury and disease.

scholarly journals Big data and single cell transcriptomics: implications for ontological representation

2018 ◽  
Author(s):  
Brian D. Aevermann ◽  
Mark Novotny ◽  
Trygve Bakken ◽  
Jeremy A. Miller ◽  
Alexander D. Diehl ◽  
...  
Keyword(s):  
Big Data ◽  
Single Cell ◽  
Rna Sequencing ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
The Body ◽  
Marker Genes ◽  
Cell Type ◽  
Type Classes ◽  
Cellular Phenotypes

AbstractCells are fundamental functional units of multicellular organisms, with different cell types playing distinct physiological roles in the body. The recent advent of single cell transcriptional profiling using RNA sequencing is producing “big data”, enabling the identification of novel human cell types at an unprecedented rate. In this review, we summarize recent work characterizing cell types in the human central nervous and immune systems using single cell and single nuclei RNA sequencing, and discuss the implications that these discoveries are having on the representation of cell types in the reference Cell Ontology (CL). We propose a method based on random forest machine learning for identifying sets of necessary and sufficient marker genes that can be used to assemble consistent and reproducible cell type definitions for incorporation into the CL. The representation of defined cell type classes and their relationships in the CL using this strategy will make the cell type classes findable, accessible, interoperable, and reusable (FAIR), allowing the CL to serve as a reference knowledgebase of information about the role that distinct cellular phenotypes play in human health and disease.

Adrenergic and Cholinergic Uterine Innervation and the Impact on Reproduction in Aged Women

2020 ◽  
Vol 26 (3) ◽  
pp. 358-362 ◽  
Author(s):  
Ioannis P. Kosmas ◽  
Antonio Malvasi ◽  
Daniele Vergara ◽  
Ospan A. Mynbaev ◽  
Radmila Sparic ◽  
...  
Keyword(s):  
Negative Impact ◽  
Smooth Muscles ◽  
Nerve Fibers ◽  
The Body ◽  
Autonomous Nervous System ◽  
Childbearing Age ◽  
Assisted Reproductive Technique ◽  
Aged Patients ◽  
Post Menopause ◽  
The Impact

: In recent years, the development of Assisted Reproductive Technique, the egg and embryo donation changed substantially the role of the uterus in recent years. It provided a higher chance for a pregnancy even in women over 45 years or post-menopause. In fact, the number of aged patients and in peri/post-menopause in pregnancy is nowadays increasing, but it increases obstetrical and neonatal related problems. The human uterus is richly innervated and modified especially during pregnancy and labor, and it is endowed with different sensory, parasympathetic, sympathetic and peptidergic neurofibers. They are differently distributed in uterine fundus, body and cervix, and they are mainly observed in the stroma and around arterial vessel walls in the myometrial and endometrial layers. Many neurotransmitters playing important roles in reproductive physiology are released after stimulation by adrenergic or cholinergic nerve fibers (the so called sympathetic/parasympathetic co-transmission). Immunohistochemical study demonstrated the localization and quantitative distribution of neurofibers in the fundus, the body and cervix of young women of childbearing age. : Adrenergic and cholinergic effects of the autonomous nervous system are the most implicated in the uterine functionality. In such aged women, the Adrenergic and AChE neurofibers distribution in the fundus, body and cervix is progressively reduced by increasing age. Adrenergic and AChE neurotransmitters were closely associated with the uterine arteries and myometrial smooth muscles, and they reduced markedly by ageing. The Adrenergic and AChE neurofibers decreasing has a dramatical and negative impact on uterine physiology, as the reduction of pregnancy chance and uterine growth, and the increase of abortion risk and prematurity.

scholarly journals Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH

2021 ◽  
Vol 22 (12) ◽  
pp. 6332
Author(s):  
Nikolaos Perakakis ◽  
Pavlina Chrysafi ◽  
Michael Feigh ◽  
Sanne Skovgard Veidal ◽  
Christos S. Mantzoros
Keyword(s):  
Mouse Model ◽  
Cell Activation ◽  
Stellate Cell ◽  
Liver Steatosis ◽  
Tolerance Test ◽  
The Body ◽  
Oral Glucose ◽  
Alcoholic Fatty Liver ◽  
Metabolic Outcomes ◽  
Anti Inflammatory

Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions.

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