A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons (10X)
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ABSTRACT:
PROVIDER: PRJNA1039791 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26817535.fastq.gz | Fastqsanger.gz | |||
| SRR26817536.fastq.gz | Fastqsanger.gz | |||
| SRR26817537.fastq.gz | Fastqsanger.gz | |||
| SRR26817538.fastq.gz | Fastqsanger.gz | |||
| SRR26817539_1.fastq.gz | Fastqsanger.gz |
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Project description:The brain executes control of nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from numerous supraspinal regions to the spinal cord. Despite their physiological and clinical relevance, a comprehensive molecular characterization of SPNs is still lacking. Here, we use retrograde labeling, whole-brain imaging, and high-throughput transcriptional profiling to generate a unified brain-wide anatomic and transcriptomic atlas of adult mouse SPNs at single-cell resolution. We transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain generated by the Allen Institute for Brain Science within the BRAIN Initiative Cell Census Network (BICCN). This SPN taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus, and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) highly heterogeneous excitatory and inhibitory populations in the reticular formation with broad spinal termination patterns, thus suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain, and reticular formation for gain control of brain-spinal signals. Within each of these components, this atlas revealed additional insights. From components (2) and (3), we discovered a LIM homeobox transcription factor code that parcellates the most transcriptionally complex population, reticulospinal neurons, into five molecularly distinct and spatially segregated populations. For neurons in component (1), we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties; thus, at least two different cable lines (namely, Pvalb/Kcng4/Spp1 positive and negative) with different electrophysiological properties might underlie the transmission of brain signals to the spinal cord. Together, by integrating the anatomy, molecular identity, and physiological properties, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.
2023-12-14 | GSE247594 | GEO
Project description:A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons
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Project description:The brain executes control of nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from numerous supraspinal regions to the spinal cord. Despite their physiological and clinical relevance, a comprehensive molecular characterization of SPNs is still lacking. Here, we use retrograde labeling, whole-brain imaging, and high-throughput transcriptional profiling to generate a unified brain-wide anatomic and transcriptomic atlas of adult mouse SPNs at single-cell resolution. We transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain generated by the Allen Institute for Brain Science within the BRAIN Initiative Cell Census Network (BICCN). This SPN taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus, and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) highly heterogeneous excitatory and inhibitory populations in the reticular formation with broad spinal termination patterns, thus suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain, and reticular formation for gain control of brain-spinal signals. Within each of these components, this atlas revealed additional insights. From components (2) and (3), we discovered a LIM homeobox transcription factor code that parcellates the most transcriptionally complex population, reticulospinal neurons, into five molecularly distinct and spatially segregated populations. For neurons in component (1), we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties; thus, at least two different cable lines (namely, Pvalb/Kcng4/Spp1 positive and negative) with different electrophysiological properties might underlie the transmission of brain signals to the spinal cord. Together, by integrating the anatomy, molecular identity, and physiological properties, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.
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Project description:A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons (SmartSeq)
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Project description:The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.
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Project description:The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as a significant source of synaptic input to the spinal cord. Experimental studies have shown that gene expression in individual VLM neurons is predictive of their function. However, the molecular and cellular organization of the VLM has remained uncertain. This study aimed to create a comprehensive dataset of VLM cells using single-cell RNA sequencing in male and female mice. The dataset was enriched with targeted sequencing of spinally-projecting and adrenergic/noradrenergic VLM neurons. Based on differentially expressed genes, the resulting dataset of 114,805 VLM cells identifies 23 subtypes of neurons, excluding those in the inferior olive, and 5 subtypes of astrocytes. Spinally-projecting neurons were found to be abundant in 7 subtypes of neurons, which were validated through in-situ hybridization. These subtypes included adrenergic/noradrenergic neurons, serotonergic neurons, and neurons expressing gene markers associated with pre-motor neurons in the ventromedial medulla. Further analysis of adrenergic/noradrenergic neurons and serotonergic neurons identified 9 and 6 subtypes, respectively, within each class of monoaminergic neurons. Marker genes that identify the neural network responsible for breathing were concentrated in 2 subtypes of neurons, delineated from each other by markers for excitatory and inhibitory neurons. These datasets are available for public download and for analysis with a user friendly interface. Collectively, this study provides a fine-scale molecular identification of cells in the VLM, forming the foundation for a better understanding of the VLM's role in vital functions and motor control.
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Project description:The study was designed to identify genes regulated after spinal transection that might contribute to regenerative growth of neurons projecting from the NMLF in Zebrafish. Zebrafish were injured by surgical transection of the spinal cord at 1 mm caudal to the brainstem-spinal cord junction (Injured). Animals receiving sham surgery (identical surgical procedures without transection) served as control (Control). The nucleus of the medial longitudinal fascicle (NMLF) was laser capture microdissected from approximately 30 frozen sections. RNA was prepared, amplified, and run on Affymetrix Zebrafish arrays. Zebrafish were used because they recover swimming function after spinal transection in about 6 weeks. The NMLF has been identified as a prominent group of neurons that descend through the site of injury in the spinal cord and that regenerate after injury. Times were selected to distinguish early events from those in the timeframe of regenerative growth.
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