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Science (New York, N.Y.) Apr 2018To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method...
To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.
Topics: Animals; Brain; Cell Nucleus; Gene Expression Profiling; Gene Expression Regulation, Developmental; HEK293 Cells; Humans; Mice; NIH 3T3 Cells; Neurons; Sequence Analysis, RNA; Single-Cell Analysis; Spinal Cord; Transcriptome
PubMed: 29545511
DOI: 10.1126/science.aam8999 -
Immunity Jan 2021The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are their diverse contributions to physiology and pathophysiology. Moreover, also...
The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are their diverse contributions to physiology and pathophysiology. Moreover, also given tissues harbor macrophages in discrete anatomic locations. Functional contributions of specific cell populations can in mice be dissected using Cre recombinase-mediated mutagenesis. However, single promoter-based Cre models show limited specificity for cell types. Focusing on macrophages in the brain, we establish here a binary transgenic system involving complementation-competent NCre and CCre fragments whose expression is driven by distinct promoters: Sall1: Cxcr1 mice specifically target parenchymal microglia and compound transgenic Lyve1: Cxcr1 animals target vasculature-associated macrophages, in the brain, as well as other tissues. We imaged the respective cell populations and retrieved their specific translatomes using the RiboTag in order to define them and analyze their differential responses to a challenge. Collectively, we establish the value of binary transgenesis to dissect tissue macrophage compartments and their functions.
Topics: Animals; Brain; Cells, Cultured; Central Nervous System; Integrases; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microglia; Organ Specificity
PubMed: 33333014
DOI: 10.1016/j.immuni.2020.11.007 -
American Journal of Medical Genetics.... Aug 2013Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving...
Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the YWHAE and LIS1 genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of YWHAE and flanking genes such as CRK. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of YWHAE and CRK, or growth failure with duplications of LIS1. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; 14-3-3 Proteins; Adolescent; Adult; Brain; Child; Child Behavior Disorders; Child Development Disorders, Pervasive; Child, Preschool; Chromosomes, Human, Pair 17; Female; Gene Duplication; Humans; Infant; Male; Microtubule-Associated Proteins; Phenotype
PubMed: 23813913
DOI: 10.1002/ajmg.a.35996 -
Neuropsychology Review Jun 2020Recently, the discussion regarding the consequences of cutting the corpus callosum ("split-brain") has regained momentum (Corballis, Corballis, Berlucchi, & Marzi,... (Review)
Review
Recently, the discussion regarding the consequences of cutting the corpus callosum ("split-brain") has regained momentum (Corballis, Corballis, Berlucchi, & Marzi, Brain, 141(6), e46, 2018; Pinto et al., Brain, 140(5), 1231-1237, 2017a; Pinto, Lamme, & de Haan, Brain, 140(11), e68, 2017; Volz & Gazzaniga, Brain, 140(7), 2051-2060, 2017; Volz, Hillyard, Miller, & Gazzaniga, Brain, 141(3), e15, 2018). This collective review paper aims to summarize the empirical common ground, to delineate the different interpretations, and to identify the remaining questions. In short, callosotomy leads to a broad breakdown of functional integration ranging from perception to attention. However, the breakdown is not absolute as several processes, such as action control, seem to remain unified. Disagreement exists about the responsible mechanisms for this remaining unity. The main issue concerns the first-person perspective of a split-brain patient. Does a split-brain harbor a split consciousness or is consciousness unified? The current consensus is that the body of evidence is insufficient to answer this question, and different suggestions are made with respect to how future studies might address this paucity. In addition, it is suggested that the answers might not be a simple yes or no but that intermediate conceptualizations need to be considered.
Topics: Attention; Consciousness; Corpus Callosum; Humans; Split-Brain Procedure
PubMed: 32399946
DOI: 10.1007/s11065-020-09439-3 -
Cortex; a Journal Devoted To the Study... Mar 2020In 'split-brain' patients, the corpus callosum has been surgically severed to alleviate medically intractable, severe epilepsy. The classic claim is that after removal... (Review)
Review
In 'split-brain' patients, the corpus callosum has been surgically severed to alleviate medically intractable, severe epilepsy. The classic claim is that after removal of the corpus callosum an object presented in the right visual field will be identified correctly verbally and with the right hand but not with the left hand. When the object is presented in the left visual field the patient verbally states that he saw nothing but nevertheless identifies it accurately with the left hand. This interaction suggests that perception, recognition and responding are separated in the two isolated hemispheres. However, there is now accumulating evidence that this interaction is not absolute. Recently, we (Pinto et al., 2017) showed that accurate detection and location of stimuli anywhere in the visual field could be performed with both hands. In this study, we explored detection and localisation of tactile stimulation on the body. In line with our previous results, we observed that split-brain patients can signal detection and localisation with either hand anywhere on the body (be it the arm or the leg) but they remain unable to match positions touched on both arms or legs simultaneously. These results add to the evidence suggesting that the effects of removal of the corpus callosum may be less severe than sometimes claimed.
Topics: Corpus Callosum; Functional Laterality; Hand; Humans; Male; Split-Brain Procedure; Touch
PubMed: 31923846
DOI: 10.1016/j.cortex.2019.11.010 -
Brain : a Journal of Neurology Aug 2022This scientific commentary refers to ‘Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline’ by Rabin...
This scientific commentary refers to ‘Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline’ by Rabin (https://doi.org/10.1093/brain/awac178).
Topics: Alzheimer Disease; Amyloid; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Cognitive Dysfunction; Humans; Plaque, Amyloid
PubMed: 35848864
DOI: 10.1093/brain/awac228 -
Journal of Neuropsychology Mar 2021In common sense experience based on introspection, consciousness is singular. There is only one 'me' and that is the one that is conscious. This means that 'singularity'... (Review)
Review
In common sense experience based on introspection, consciousness is singular. There is only one 'me' and that is the one that is conscious. This means that 'singularity' is a defining aspect of 'consciousness'. However, the three main theories of consciousness, Integrated Information, Global Workspace and Recurrent Processing theory, are generally not very clear on this issue. These theories have traditionally relied heavily on neuropsychological observations and have interpreted various disorders, such as anosognosia, neglect and split-brain as impairments in conscious awareness without any reference to 'the singularity'. In this review, we will re-examine the theoretical implications of these impairments in conscious awareness and propose a new way how to conceptualize consciousness of singularity. We will argue that the subjective feeling of singularity can coexist with several disunified conscious experiences. Singularity awareness may only come into existence due to environmental response constraints. That is, perceptual, language, memory, attentional and motor processes may largely proceed unintegrated in parallel, whereas a sense of unity only arises when organisms need to respond coherently constrained by the affordances of the environment. Next, we examine from this perspective psychiatric disorders and psycho-active drugs. Finally, we present a first attempt to test this hypothesis with a resting state imaging experiment in a split-brain patient. The results suggest that there is substantial coherence of activation across the two hemispheres. These data show that a complete lesioning of the corpus callosum does not, in general, alter the resting state networks of the brain. Thus, we propose that we have separate systems in the brain that generate distributed conscious. The sense of singularity, the experience of a 'Me-ness', emerges in the interaction between the world and response-planning systems, and this leads to coherent activation in the different functional networks across the cortex.
Topics: Attention; Brain; Consciousness; Humans; Split-Brain Procedure
PubMed: 33522716
DOI: 10.1111/jnp.12234 -
Acta Clinica Croatica Dec 2018- A case of a 37-year-old female patient is presented. The patient was admitted to the Surgical Emergency Unit after accidental fall on a metal rod when she had...
- A case of a 37-year-old female patient is presented. The patient was admitted to the Surgical Emergency Unit after accidental fall on a metal rod when she had sustained stab injury of the right orbit with penetration into the right frontal brain lobe. Multi-slice computed tomography (MSCT) showed penetrating injury and fracture of the right orbital roof without eyeball damage and endocranial impressed bone fragments into the right frontal brain lobe. Urgent surgical intervention was performed by a maxillofacial surgeon and neurosurgeon, including reposition of bone fragments of the orbital roof and cranioplasty. Reconstruction of Tenon's capsule of the right eyeball was performed by an ophthalmologist. From the intraoperative wound swab of the orbit, was isolated, therefore the patient was administered ciprofloxacin and rifampicin as recommended by an infectious disease (ID) specialist. Follow up brain MSCT at 15 days and magnetic resonance imaging of the brain at 25 days showed brain edema in the right frontal area and signs of local brain abscess. Intravenous administration of the ciprofloxacin and metronidazole antibiotics with corticosteroids for edema suppression were ordered by the ID physician. Fourteen weeks after this therapy, brain MSCT showed complete abscess regression and no neurologic deficit with only mild psychomotor changes.
Topics: Adult; Anti-Bacterial Agents; Brain Abscess; Eye Injuries; Female; Fracture Fixation; Humans; Magnetic Resonance Imaging; Neurosurgical Procedures; Ophthalmologic Surgical Procedures; Orbit; Orbital Fractures; Postoperative Complications; Skull; Tomography, X-Ray Computed; Treatment Outcome; Wounds, Penetrating
PubMed: 31168221
DOI: 10.20471/acc.2018.57.04.26 -
Personality Neuroscience 2020Brain laterality refers to the asymmetric location of functional elements within the bilateral brain of animals and humans. Thus far, five lateralized functions have...
Brain laterality refers to the asymmetric location of functional elements within the bilateral brain of animals and humans. Thus far, five lateralized functions have been recognized in humans: handedness, language ability, spatial skills, facial recognition, and emotion recognition. Recently, a sixth asymmetric functional element bearing on personality has been discovered. It is the larger side of the split bilateral anterior cingulate cortex (ACC). This appears to be the final output element of the executive system of which, by logic, there can be only one. Which side is somewhat larger varies among the general population in a seemingly idiosyncratic manner, yet with a genetic basis because true-breeding lineages exist. Here, hemisity is binary measure where a person is inherently born right brain or left brain oriented. This is determined by nine statistically robust sets of four biophysical tests, none of which depend upon personality, and five behavioral questionnaires. Crucially these hemisity methods have been validated by the Magnetic Resonance Imaging (MRI)-based discovery that the larger side of the ACC is on the same side as one's hemisity, making MRI the primary standard for hemisity determination ( = 0.96). There are at least 30 measurable differences in individual characteristics and behaviors between those persons whose hemsity is on the right compared to those with it on the left. The hemisity of 2929 individuals was determined by these methods. Large groups included 1428 junior and senior high schools students both in Hawaii and Utah. There were somewhat comparable numbers present for both types of hemisity. Hemisity of individuals was found stable from infancy to old age. There was no relation between hemisity and handedness. Larger corpus callosum (CC) size of male or female subjects was larger in right brainer that in left brainers. Twin studies demonstrate that CC size is inherited. Thirty-eight percent of individuals of both sexes were right brain oriented, while 62% of individuals of both sexes were left brain oriented. In pairings, there were more than twice as many couples with opposite hemisity. Of these couples, the right brain male and females were dominant. Reproductive outcomes of these were "Like father like son, Like mother like daughter."
PubMed: 33134808
DOI: 10.1017/pen.2020.6 -
Neuroscience Research Dec 2021The astrocyte is a central glial cell and plays a critical role in the architecture and activity of neuronal circuits and brain functions through forming a tripartite... (Review)
Review
The astrocyte is a central glial cell and plays a critical role in the architecture and activity of neuronal circuits and brain functions through forming a tripartite synapse with neurons. Emerging evidence suggests that dysfunction of tripartite synaptic connections contributes to a variety of psychiatric and neurodevelopmental disorders. Furthermore, recent advancements with transcriptome profiling, cell biological and physiological approaches have provided new insights into the molecular mechanisms into how astrocytes control synaptogenesis in the brain. In addition to these findings, we have recently developed in vivo cell-surface proximity-dependent biotinylation (BioID) approaches, TurboID-surface and Split-TurboID, to comprehensively understand the molecular composition between astrocytes and neuronal synapses. These proteomic approaches have discovered a novel molecular framework for understanding the tripartite synaptic cleft that arbitrates neuronal circuit formation and function. Here, this short review highlights novel in vivo cell-surface BioID approaches and recent advances in this rapidly evolving field, emphasizing how astrocytes regulate excitatory and inhibitory synapse formation in vitro and in vivo.
Topics: Astrocytes; Neurogenesis; Neurons; Proteomics; Synapses
PubMed: 34019951
DOI: 10.1016/j.neures.2021.05.002