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Human motor neurons are rare in the spinal cord and can be transcriptomically divided into known subtypes divided into known subtypes.

ABSTRACT: Human motor neurons are rare in the spinal cord and can be transcriptomically divided into known subtypes divided into known subtypes.

PROVIDER: PRJNA951608 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24045555_1.fastq.gz	Fastqsanger.gz
	SRR24045555_2.fastq.gz	Fastqsanger.gz
	SRR24045556_1.fastq.gz	Fastqsanger.gz
	SRR24045556_2.fastq.gz	Fastqsanger.gz
	SRR24045557_1.fastq.gz	Fastqsanger.gz

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Human motor neurons are rare in the spinal cord and can be transcriptomically divided into known subtypes divided into known subtypes.

Project description:Motor neurons are a rare neuronal subtype in the adult spinal cord. We performed single-nucleus RNA sequencing on nuclei extracted from adult human spinal cord and describe the transcriptional heterogeneity.

2023-04-06 | GSE228778 | GEO

Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord

Project description:We developed a targeted single nucleus RNA sequencing approach to enrich and transcriptomically characterize cholinergic neurons of the adult mouse spinal cord. Our data expose markers for known classes of cholinergic neurons and their extremely rich diversity. Visceral/preganglionic motor neurons could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor neurons was also reflected in our analysis with alpha, gamma, and a third subtype clearly distinguished. We further identified previously unrecognized subtypes of cholinergic interneurons.

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Graded arrays of spinal and supraspinal V2a interneuron subtypes underlie forelimb and hindlimb motor control [RNA-seq]

Project description:The spinal cord contains neural networks that enable regionally-distinct motor outputs along the body axis. Nevertheless, it remains unclear how segment-specific motor computations are processed because the cardinal interneuron classes that control motor neurons appear uniform at each level of the spinal cord. V2a interneurons are essential to both fore and hindlimb movements and here we identified two major types that emerge during development: Type-I neurons marked by high Chx10 form recurrent networks with neighboring spinal neurons, and Type-II that downregulate Chx10 and project to supraspinal structures. Type-I and -II V2a interneurons are arrayed in counter-gradients and this network activates different patterns of motor output at cervical and lumbar levels. Single cell RNA-seq revealed Type-I and -II V2a neurons are each comprised of multiple subtypes. Our findings uncover a molecular and anatomical organization of V2a interneurons reminiscent of the orderly way motor neurons are divided into columns and pools.

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Graded arrays of spinal and supraspinal V2a interneuron subtypes underlie forelimb and hindlimb motor control [scRNA-seq]

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Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed

Project description:Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally-distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific features during development. Using single-cell RNA profiling in embryonic and larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes, and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily-conserved transcription factors, Prdm16 and Mecom, are both functional subtype-specific determinants integral for fast MN development. Loss of prdm16 or mecom causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate axial MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.

2023-08-24 | GSE240026 | GEO

Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed

Project description:Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed

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Single cell RNAseq analysis in embryonic spinal cords to profile transcriptomes in control and Jmjd3cKO motor neurons.

Project description:To characterize Jmjd3 function in motor neuron development, we isolated GFP+ cells derived from Olig2 expressing progenitor cells that included motor neuron population and then employed single cell RNAseq. We found some novel motor neuron subtypes in addition to well-known motor columns, and specific genes in each subtype by unbiased and comprehensive analysis. Moreover, by comparing control and Jmjd3cKO motor neuron lineage cells, we found many downregulated and upregulated genes affected by Jmjd3 loss of function. Single cell RNAseq provided very powerful tool to analyze different regulated genes in each subtype rather than overall motor neuron groups.

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Gene expression profiling of resistant and vulnerable motor neuron subtypes in amyotrophic lateral sclerosis

Project description:A consistent clinical feature of amyotrophic lateral sclerosis (ALS) is the sparing of eye movements. Pathological studies have confirmed that there is relative sparing of the cranial motor nuclei of the oculomotor, trochlear and abducens nerves, although pathological changes resembling those seen in anterior horn cells are present to a lesser degree. The aim of the present study is to combine LCM and microarray analysis to study the differences between motor neurons that are selectively resistant (oculomotor neurons) and those that are vulnerable (lumbar spinal motor neurons) to the disease process in amyotrophic lateral sclerosis. We used microarray analysis to determine the differences in gene expression between oculomotor and lumbar spinal motor neurons, isolated by laser capture microdissection from the midbrain and spinal cord of neurologically normal human controls.

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Project description:Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are a strong genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at the cellular and functional level remains unknown. Here, we developed a human iPSC-derived model to investigate whether motor neurons derived from ALS patients carrying ATXN2 intermediate repeat expansions are transcriptomically distinct from healthy controls. For that, we performed RNA sequencing of motor neurons derived from 5 ATXN2-ALS iPSC lines and 5 healthy controls (HC).

2024-07-16 | GSE224578 | GEO

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