Cell type specificity of glucocorticoid signaling in the adult mouse hippocampus

Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1) and the mineralocorticoid receptor (MR: Nr3c2). These nuclear steroid...

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Published inJournal of neuroendocrinology Vol. 34; no. 2; pp. e13072 - n/a
Main Authors Viho, Eva M. G., Buurstede, Jacobus C., Berkhout, Jari B., Mahfouz, Ahmed, Meijer, Onno C.
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.02.2022
John Wiley and Sons Inc
Subjects
Cognitive ability
corticosteroid receptors
Gene expression
Glucocorticoids
Hippocampus
Neuromodulation
Neuropeptides
Neurotransmitters
Original
Sex hormones
single‐cell RNA sequencing
Steroid hormone receptors
stress hormones
Transcription factors
transcription regulation
single-cell RNA sequencing
corticosteroid receptors
transcription regulation
stress hormones
hippocampus
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Abstract Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1) and the mineralocorticoid receptor (MR: Nr3c2). These nuclear steroid receptors act as ligand‐dependent transcription factors. Transcriptional effects of glucocorticoids have often been deduced from bulk mRNA measurements or spatially informed individual gene expression. However, only sparse data exists allowing insights on glucocorticoid‐driven gene transcription at the cell type level. Here, we used publicly available single‐cell RNA sequencing data to assess the cell‐type specificity of GR and MR signaling in the adult mouse hippocampus. The data confirmed that Nr3c1 and Nr3c2 expression differs across neuronal and non‐neuronal cell populations. We analyzed co‐expression with sex hormones receptors, transcriptional coregulators, and receptors for neurotransmitters and neuropeptides. Our results provide insights in the cellular basis of previous bulk mRNA results and allow the formulation of more defined hypotheses on the effects of glucocorticoids on hippocampal function.
AbstractList Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1 ) and the mineralocorticoid receptor (MR: Nr3c2 ). These nuclear steroid receptors act as ligand‐dependent transcription factors. Transcriptional effects of glucocorticoids have often been deduced from bulk mRNA measurements or spatially informed individual gene expression. However, only sparse data exists allowing insights on glucocorticoid‐driven gene transcription at the cell type level. Here, we used publicly available single‐cell RNA sequencing data to assess the cell‐type specificity of GR and MR signaling in the adult mouse hippocampus. The data confirmed that Nr3c1 and Nr3c2 expression differs across neuronal and non‐neuronal cell populations. We analyzed co‐expression with sex hormones receptors, transcriptional coregulators, and receptors for neurotransmitters and neuropeptides. Our results provide insights in the cellular basis of previous bulk mRNA results and allow the formulation of more defined hypotheses on the effects of glucocorticoids on hippocampal function.
Abstract Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1 ) and the mineralocorticoid receptor (MR: Nr3c2 ). These nuclear steroid receptors act as ligand‐dependent transcription factors. Transcriptional effects of glucocorticoids have often been deduced from bulk mRNA measurements or spatially informed individual gene expression. However, only sparse data exists allowing insights on glucocorticoid‐driven gene transcription at the cell type level. Here, we used publicly available single‐cell RNA sequencing data to assess the cell‐type specificity of GR and MR signaling in the adult mouse hippocampus. The data confirmed that Nr3c1 and Nr3c2 expression differs across neuronal and non‐neuronal cell populations. We analyzed co‐expression with sex hormones receptors, transcriptional coregulators, and receptors for neurotransmitters and neuropeptides. Our results provide insights in the cellular basis of previous bulk mRNA results and allow the formulation of more defined hypotheses on the effects of glucocorticoids on hippocampal function.
Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent glucocorticoid target and expresses both the glucocorticoid receptor (GR: Nr3c1) and the mineralocorticoid receptor (MR: Nr3c2). These nuclear steroid receptors act as ligand‐dependent transcription factors. Transcriptional effects of glucocorticoids have often been deduced from bulk mRNA measurements or spatially informed individual gene expression. However, only sparse data exists allowing insights on glucocorticoid‐driven gene transcription at the cell type level. Here, we used publicly available single‐cell RNA sequencing data to assess the cell‐type specificity of GR and MR signaling in the adult mouse hippocampus. The data confirmed that Nr3c1 and Nr3c2 expression differs across neuronal and non‐neuronal cell populations. We analyzed co‐expression with sex hormones receptors, transcriptional coregulators, and receptors for neurotransmitters and neuropeptides. Our results provide insights in the cellular basis of previous bulk mRNA results and allow the formulation of more defined hypotheses on the effects of glucocorticoids on hippocampal function.
Author Berkhout, Jari B.
Viho, Eva M. G.
Mahfouz, Ahmed
Meijer, Onno C.
Buurstede, Jacobus C.
AuthorAffiliation 3 Department of Human Genetics Leiden University Medical Center Leiden The Netherlands
5 Leiden Computational Biology Center Leiden University Medical Center Leiden The Netherlands
1 Division of Endocrinology Department of Medicine Leiden University Medical Center Leiden The Netherlands
4 Delft Bioinformatics Laboratory Delft University of Technology Delft The Netherlands
2 Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Center Leiden The Netherlands
AuthorAffiliation_xml – name: 5 Leiden Computational Biology Center Leiden University Medical Center Leiden The Netherlands
– name: 2 Einthoven Laboratory for Experimental Vascular Medicine Leiden University Medical Center Leiden The Netherlands
– name: 3 Department of Human Genetics Leiden University Medical Center Leiden The Netherlands
– name: 4 Delft Bioinformatics Laboratory Delft University of Technology Delft The Netherlands
– name: 1 Division of Endocrinology Department of Medicine Leiden University Medical Center Leiden The Netherlands
Author_xml – sequence: 1
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  surname: Viho
  fullname: Viho, Eva M. G.
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  organization: Leiden University Medical Center
– sequence: 2
  givenname: Jacobus C.
  surname: Buurstede
  fullname: Buurstede, Jacobus C.
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  surname: Meijer
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Keywords single-cell RNA sequencing
corticosteroid receptors
transcription regulation
stress hormones
hippocampus
Language English
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Snippet Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent...
Abstract Glucocorticoid stress hormones are powerful modulators of brain function and can affect mood and cognitive processes. The hippocampus is a prominent...
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SubjectTerms Cognitive ability
corticosteroid receptors
Gene expression
Glucocorticoids
Hippocampus
Neuromodulation
Neuropeptides
Neurotransmitters
Original
Sex hormones
single‐cell RNA sequencing
Steroid hormone receptors
stress hormones
Transcription factors
transcription regulation
Title Cell type specificity of glucocorticoid signaling in the adult mouse hippocampus
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fjne.13072
https://www.ncbi.nlm.nih.gov/pubmed/34939259
https://www.proquest.com/docview/2631797814
https://search.proquest.com/docview/2613291644
https://pubmed.ncbi.nlm.nih.gov/PMC9286676
Volume 34
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