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Transcriptomic atlas of thalamic nuclei

ABSTRACT: Transcriptomic atlas of thalamic nuclei

PROVIDER: PRJNA552996 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9649610.fastq.gz	Fastqsanger.gz
	SRR9649620.fastq.gz	Fastqsanger.gz
	SRR9649630.fastq.gz	Fastqsanger.gz
	SRR9649640.fastq.gz	Fastqsanger.gz
	SRR9649650.fastq.gz	Fastqsanger.gz

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Transcriptomic atlas of thalamic nuclei

Project description:We profiled the transcriptome of 22 thalamic nuclei. Nuclei were retrogradely labeled from their forebrain target areas, microdissected and fluorescent cells pooled. Anterograde tracing was used when identification of nuclear boundaries was ambiguous. We found that thalamic nuclei share a common axis of variance closely linked to the mediolateral spatial axis of thalamus. This axis was enriched in functionally relevant genes such as neurotransmitter receptors and ion channels, and was closely linked to functional and morphological properties of the neurons.

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Project description:We collected single-cell RNAseq data from neurons of five thalamocortical projection systems (motor, somatosensory, visual, auditory, and prefrontal). Cells of each projection system were retrogradely labeled from their cortical target area, microdissected, and collected individually. By combining single-cell transcriptomics with in situ RNA hybridization, we found heterogeneity not only between thalamic nuclei but also within nuclei, with graded transitions between cell identities.

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Project description:The thalamus is the principal information hub of the vertebrate brain, with essential roles in sensory and motor information processing, attention, and memory. The complex array of thalamic nuclei develops from a restricted pool of neural progenitors. We apply longitudinal single-cell RNA-sequencing and regional abrogation of Sonic hedgehog (Shh) to map the developmental trajectories of thalamic progenitors, intermediate progenitors, and post-mitotic neurons as they coalesce into distinct thalamic nuclei. These data reveal that the complex architecture of the thalamus is established early during embryonic brain development through the coordinated action of four cell differentiation lineages derived from Shh-dependent and independent progenitors. We systematically characterize the gene expression programs that define these thalamic lineages across time and demonstrate how their disruption upon Shh depletion causes pronounced locomotor impairment resembling infantile Parkinson’s disease. These results reveal key principles of thalamic development and provide mechanistic insights into neurodevelopmental disorders resulting from thalamic dysfunction.

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Project description:The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, is known to regulate thalamocortical interactions critical for sensory processing, attention and cognition. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders. Currently, little is known about the organizational principles underlying its divergent functions. We performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that TRN cellular heterogeneity is characterized by a transcriptomic gradient of two negatively correlated gene expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core/shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections to the functionally distinct first-order and higher order thalamic nuclei to form molecularly defined TRN-thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. Taken together, our study provides a comprehensive atlas for TRN neurons at the single-cell resolution, and links molecularly defined subnetworks to the functional organization of the thalamo-cortical circuits.

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