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BioRxiv : the Preprint Server For... Apr 2023The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While previous studies have...
The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While previous studies have mainly focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 535,941 cells from 62 women, and 120,024 nuclei from 20 women, identifying 11 major cell types and 53 cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Our spatial mapping using three technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells in the ducts and lobules, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of adult normal breast tissue for studying mammary biology and disease states such as breast cancer.
PubMed: 37163043
DOI: 10.1101/2023.04.22.537946 -
Nature Jan 2021The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from...
The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from the gut. In liver lobules, blood flows from portal triads that are situated in periportal lobular regions to the central vein via a polarized sinusoidal network. Despite this asymmetry, resident immune cells in the liver are considered to be broadly dispersed across the lobule. This differs from lymphoid organs, in which immune cells adopt spatially biased positions to promote effective host defence. Here we used quantitative multiplex imaging, genetic perturbations, transcriptomics, infection-based assays and mathematical modelling to reassess the relationship between the localization of immune cells in the liver and host protection. We found that myeloid and lymphoid resident immune cells concentrate around periportal regions. This asymmetric localization was not developmentally controlled, but resulted from sustained MYD88-dependent signalling induced by commensal bacteria in liver sinusoidal endothelial cells, which in turn regulated the composition of the pericellular matrix involved in the formation of chemokine gradients. In vivo experiments and modelling showed that this immune spatial polarization was more efficient than a uniform distribution in protecting against systemic bacterial dissemination. Together, these data reveal that liver sinusoidal endothelial cells sense the microbiome, actively orchestrating the localization of immune cells, to optimize host defence.
Topics: Animals; Bacteria; Cell Separation; Chemokine CXCL9; Endothelial Cells; Female; Gastrointestinal Microbiome; Humans; Kupffer Cells; Liver; Lymphocytes; Male; Mice; Models, Immunological; Molecular Imaging; Myeloid Cells; Myeloid Differentiation Factor 88; Signal Transduction; Symbiosis; Transcriptome
PubMed: 33239787
DOI: 10.1038/s41586-020-2977-2 -
Frontiers in Neurology 2021Vestibular and optokinetic space is represented in three-dimensions in vermal lobules IX-X (uvula, nodulus) and hemisphere lobule X (flocculus) of the cerebellum. Vermal... (Review)
Review
Vestibular and optokinetic space is represented in three-dimensions in vermal lobules IX-X (uvula, nodulus) and hemisphere lobule X (flocculus) of the cerebellum. Vermal lobules IX-X encodes gravity and head movement using the utricular otolith and the two vertical semicircular canals. Hemispheric lobule X encodes self-motion using optokinetic feedback about the three axes of the semicircular canals. Vestibular and visual adaptation of this circuitry is needed to maintain balance during perturbations of self-induced motion. Vestibular and optokinetic (self-motion detection) stimulation is encoded by cerebellar climbing and mossy fibers. These two afferent pathways excite the discharge of Purkinje cells directly. Climbing fibers preferentially decrease the discharge of Purkinje cells by exciting stellate cell inhibitory interneurons. We describe instances adaptive balance at a behavioral level in which prolonged vestibular or optokinetic stimulation evokes reflexive eye movements that persist when the stimulation that initially evoked them stops. Adaptation to prolonged optokinetic stimulation also can be detected at cellular and subcellular levels. The transcription and expression of a neuropeptide, corticotropin releasing factor (CRF), is influenced by optokinetically-evoked olivary discharge and may contribute to optokinetic adaptation. The transcription and expression of microRNAs in floccular Purkinje cells evoked by long-term optokinetic stimulation may provide one of the subcellular mechanisms by which the membrane insertion of the GABAA receptors is regulated. The neurosteroids, estradiol (E2) and dihydrotestosterone (DHT), influence adaptation of vestibular nuclear neurons to electrically-induced potentiation and depression. In each section of this review, we discuss how adaptive changes in the vestibular and optokinetic subsystems of lobule X, inferior olivary nuclei and vestibular nuclei may contribute to the control of balance.
PubMed: 33767662
DOI: 10.3389/fneur.2021.635259 -
Hepatology (Baltimore, Md.) May 2024Hepatocytes work in highly structured, repetitive hepatic lobules. Blood flow across the radial axis of the lobule generates oxygen, nutrient, and hormone gradients,... (Review)
Review
Hepatocytes work in highly structured, repetitive hepatic lobules. Blood flow across the radial axis of the lobule generates oxygen, nutrient, and hormone gradients, which result in zoned spatial variability and functional diversity. This large heterogeneity suggests that hepatocytes in different lobule zones may have distinct gene expression profiles, metabolic features, regenerative capacity, and susceptibility to damage. Here, we describe the principles of liver zonation, introduce metabolomic approaches to study the spatial heterogeneity of the liver, and highlight the possibility of exploring the spatial metabolic profile, leading to a deeper understanding of the tissue metabolic organization. Spatial metabolomics can also reveal intercellular heterogeneity and its contribution to liver disease. These approaches facilitate the global characterization of liver metabolic function with high spatial resolution along physiological and pathological time scales. This review summarizes the state of the art for spatially resolved metabolomic analysis and the challenges that hinder the achievement of metabolome coverage at the single-cell level. We also discuss several major contributions to the understanding of liver spatial metabolism and conclude with our opinion on the future developments and applications of these exciting new technologies.
Topics: Humans; Liver; Hepatocytes; Liver Diseases; Transcriptome; Metabolomics
PubMed: 36811413
DOI: 10.1097/HEP.0000000000000341 -
Clinical Neurophysiology Practice 2022The human cerebellum contains more than 60% of all neurons of the brain. Anatomically, the cerebellum is divided into 10 lobules (I-X). The cerebellar cortex is arranged... (Review)
Review
The human cerebellum contains more than 60% of all neurons of the brain. Anatomically, the cerebellum is divided into 10 lobules (I-X). The cerebellar cortex is arranged into three layers: the molecular layer (external), the Purkinje cell layer and the granular layer (internal). Purkinje neurons and interneurons are inhibitory, except for granule cells. The layer of Purkinje neurons inhibit cerebellar nuclei, the sole output of the cerebellar circuitry, as well as vestibular nuclei. The cerebellum is arranged into a series of olivo-cortico-nuclear modules arranged longitudinally in the rostro-caudal plane. The cerebro-cerebellar connectivity is organized into multiple loops running in parallel. From the clinical standpoint, it is now considered that cerebellar symptoms can be gathered into 3 cerebellar syndromes: a cerebellar motor syndrome (CMS), a vestibulocerebellar syndrome (VCS) and a cerebellar cognitive affective syndrome/Schmahmann syndrome (CCAS/SS). CMS remains a cornerstone of modern clinical ataxiology, and relevant lesions involve lobules I-V, VI and VIII. The core feature of cerebellar symptoms is dysmetria, covering motor dysmetria (errors in the metrics of motion) and dysmetria of thought. The cerebellar circuitry plays a key-role in the generation and maintenance of internal models which correspond to neural representations reproducing the dynamic properties of the body. These models allow predictive computations for motor, cognitive, social, and affective operations. Cerebellar circuitry is endowed with noticeable plasticity properties.
PubMed: 36504687
DOI: 10.1016/j.cnp.2022.11.002 -
Insights Into Imaging Aug 2019There has been an increasing demand and interest in post-mortem imaging techniques, either as an adjunct or replacement for the conventional invasive autopsy.... (Review)
Review
There has been an increasing demand and interest in post-mortem imaging techniques, either as an adjunct or replacement for the conventional invasive autopsy. Post-mortem ultrasound (PMUS) is easily accessible and more affordable than other cross-sectional imaging modalities and allows visualisation of normal anatomical structures of the brain, thorax and abdomen in perinatal cases. The lack of aeration of post-mortem foetal lungs provides a good sonographic window for assessment of the heart and normal pulmonary lobulation, in contrast to live neonates.In a previous article within this journal, we published a practical approach to conducting a comprehensive PMUS examination. This covered the basic principles behind why post-mortem imaging is performed, helpful techniques for obtaining optimal PMUS images, and the expected normal post-mortem changes seen in perinatal deaths. In this article, we build upon this by focusing on commonly encountered pathologies on PMUS and compare these to autopsy and other post-mortem imaging modalities.
PubMed: 31432284
DOI: 10.1186/s13244-019-0762-2 -
International Journal of Emergency... Oct 2020This is a brief report of a 57-year-old Caucasian female presented with a 4-day history of worsening left ear pain. Her symptoms began with left otalgia and otorrhea...
CASE PRESENTATION
This is a brief report of a 57-year-old Caucasian female presented with a 4-day history of worsening left ear pain. Her symptoms began with left otalgia and otorrhea which progressed to helical erythema, prompting a visit to the emergency department. She was noted to have erythema of the left auricle and swelling of the left auditory meatus. Our otolaryngology service observed erythema of the auricle with sparing of the lobule.
DIAGNOSIS
The diagnosis to be otitis externa with perichondritis was established, and we recommended otic ciprofloxacin-hydrocortisone, IV vancomycin, and ciprofloxacin. The patient had marked improvement and was discharged on an oral and otic fluoroquinolone. In this case, the diagnosis of perichondritis was made by a classic physical examination finding: erythema and edema with sparing of the fatty lobule. This key finding helps to distinguish perichondritis from otitis externa.
PubMed: 33115411
DOI: 10.1186/s12245-020-00310-z