Dataset Information

Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment.

ABSTRACT:

Objective

Growth differentiation factor 15 (GDF15) is known to play a role in feeding, nausea, and body weight, with action through the GFRAL-RET receptor complex in the area postrema (AP) and nucleus tractus solitarius (NTS). To further elucidate the underlying cell type-specific molecular mechanisms downstream of GDF15 signaling, we used a single nuclei RNA sequencing (snRNAseq) approach to profile AP and NTS cellular subtype-specific transcriptomes after systemic GDF15 treatment.

Methods

AP and NTS micropunches were used for snRNAseq from Sprague Dawley rats 6 h following GDF15 or saline injection, and Seurat was used to identify cellular subtypes and cell type-specific alterations in gene expression that were due to the direct and secondary effects of systemic GDF15 treatment.

Results

Using the transcriptome profile of ∼35,000 individual AP/NTS nuclei, we identified 19 transcriptomically distinct cellular subtypes, including a single population Gfral and Ret positive excitatory neurons, representing the primary site of action for GDF15. A total of ∼600 cell type-specific differential expression events were identified in neurons and glia, including the identification of transcriptome alterations specific to the direct effects of GDF15 in the Gfral-Ret positive excitatory neurons and shared transcriptome alterations across neuronal and glial cell types. Downstream analyses identified shared and cell type-specific alterations in signaling pathways and upstream regulatory mechanisms of the observed transcriptome alterations.

Conclusions

These data provide a considerable advance in our understanding of AP and NTS cell type-specific molecular mechanisms associated with GDF15 signaling. The identified cellular subtype-specific regulatory mechanism and signaling pathways likely represent important targets for future pharmacotherapies.

SUBMITTER: Reiner BC

PROVIDER: S-EPMC8749158 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment.

Reiner Benjamin C BC Crist Richard C RC Borner Tito T Doyle Robert P RP Hayes Matthew R MR De Jonghe Bart C BC

Molecular metabolism 20211221

<h4>Objective</h4>Growth differentiation factor 15 (GDF15) is known to play a role in feeding, nausea, and body weight, with action through the GFRAL-RET receptor complex in the area postrema (AP) and nucleus tractus solitarius (NTS). To further elucidate the underlying cell type-specific molecular mechanisms downstream of GDF15 signaling, we used a single nuclei RNA sequencing (snRNAseq) approach to profile AP and NTS cellular subtype-specific transcriptomes after systemic GDF15 treatment.<h4>M ...[more]

PMID: 34942400

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Dataset Information

Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment.

Objective

Methods

Results

Conclusions

Publications

Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment.

Similar Datasets

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