Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension
A common preclinical model of hypertension characterized by low circulating renin is the “deoxycorticosterone acetate (DOCA)-salt” model, which influences blood pressure and metabolism through mechanisms involving the angiotensin II type 1 receptor (AT1R) in the brain. More specifically, AT1R within...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1207350/full |
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| author | Valerie A. Wagner Valerie A. Wagner Guorui Deng Kristin E. Claflin McKenzie L. Ritter Huxing Cui Huxing Cui Huxing Cui Pablo Nakagawa Pablo Nakagawa Curt D. Sigmund Curt D. Sigmund Curt D. Sigmund Lisa L. Morselli Justin L. Grobe Justin L. Grobe Justin L. Grobe Justin L. Grobe Justin L. Grobe Anne E. Kwitek Anne E. Kwitek Anne E. Kwitek Anne E. Kwitek |
| author_facet | Valerie A. Wagner Valerie A. Wagner Guorui Deng Kristin E. Claflin McKenzie L. Ritter Huxing Cui Huxing Cui Huxing Cui Pablo Nakagawa Pablo Nakagawa Curt D. Sigmund Curt D. Sigmund Curt D. Sigmund Lisa L. Morselli Justin L. Grobe Justin L. Grobe Justin L. Grobe Justin L. Grobe Justin L. Grobe Anne E. Kwitek Anne E. Kwitek Anne E. Kwitek Anne E. Kwitek |
| author_sort | Valerie A. Wagner |
| collection | DOAJ |
| description | A common preclinical model of hypertension characterized by low circulating renin is the “deoxycorticosterone acetate (DOCA)-salt” model, which influences blood pressure and metabolism through mechanisms involving the angiotensin II type 1 receptor (AT1R) in the brain. More specifically, AT1R within Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) has been implicated in selected effects of DOCA-salt. In addition, microglia have been implicated in the cerebrovascular effects of DOCA-salt and angiotensin II. To characterize DOCA-salt effects upon the transcriptomes of individual cell types within the ARC, we used single-nucleus RNA sequencing (snRNAseq) to examine this region from male C57BL/6J mice that underwent sham or DOCA-salt treatment. Thirty-two unique primary cell type clusters were identified. Sub-clustering of neuropeptide-related clusters resulted in identification of three distinct AgRP subclusters. DOCA-salt treatment caused subtype-specific changes in gene expression patterns associated with AT1R and G protein signaling, neurotransmitter uptake, synapse functions, and hormone secretion. In addition, two primary cell type clusters were identified as resting versus activated microglia, and multiple distinct subtypes of activated microglia were suggested by sub-cluster analysis. While DOCA-salt had no overall effect on total microglial density within the ARC, DOCA-salt appeared to cause a redistribution of the relative abundance of activated microglia subtypes. These data provide novel insights into cell-specific molecular changes occurring within the ARC during DOCA-salt treatment, and prompt increased investigation of the physiological and pathophysiological significance of distinct subtypes of neuronal and glial cell types. |
| first_indexed | 2024-03-13T09:53:24Z |
| format | Article |
| id | doaj.art-41540d841a564460be2c9f431689fc37 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-13T09:53:24Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-41540d841a564460be2c9f431689fc372023-05-24T04:34:44ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-05-011710.3389/fncel.2023.12073501207350Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertensionValerie A. Wagner0Valerie A. Wagner1Guorui Deng2Kristin E. Claflin3McKenzie L. Ritter4Huxing Cui5Huxing Cui6Huxing Cui7Pablo Nakagawa8Pablo Nakagawa9Curt D. Sigmund10Curt D. Sigmund11Curt D. Sigmund12Lisa L. Morselli13Justin L. Grobe14Justin L. Grobe15Justin L. Grobe16Justin L. Grobe17Justin L. Grobe18Anne E. Kwitek19Anne E. Kwitek20Anne E. Kwitek21Anne E. Kwitek22Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesGenetics Graduate Program, University of Iowa, Iowa City, IA, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, United StatesObesity Research and Education Initiative, University of Iowa, Iowa City, IA, United StatesFraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesCardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesCardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United StatesNeuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Division of Endocrinology and Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesCardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United StatesNeuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, United StatesComprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, WI, United States0Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesCardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States0Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, United States1Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesA common preclinical model of hypertension characterized by low circulating renin is the “deoxycorticosterone acetate (DOCA)-salt” model, which influences blood pressure and metabolism through mechanisms involving the angiotensin II type 1 receptor (AT1R) in the brain. More specifically, AT1R within Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) has been implicated in selected effects of DOCA-salt. In addition, microglia have been implicated in the cerebrovascular effects of DOCA-salt and angiotensin II. To characterize DOCA-salt effects upon the transcriptomes of individual cell types within the ARC, we used single-nucleus RNA sequencing (snRNAseq) to examine this region from male C57BL/6J mice that underwent sham or DOCA-salt treatment. Thirty-two unique primary cell type clusters were identified. Sub-clustering of neuropeptide-related clusters resulted in identification of three distinct AgRP subclusters. DOCA-salt treatment caused subtype-specific changes in gene expression patterns associated with AT1R and G protein signaling, neurotransmitter uptake, synapse functions, and hormone secretion. In addition, two primary cell type clusters were identified as resting versus activated microglia, and multiple distinct subtypes of activated microglia were suggested by sub-cluster analysis. While DOCA-salt had no overall effect on total microglial density within the ARC, DOCA-salt appeared to cause a redistribution of the relative abundance of activated microglia subtypes. These data provide novel insights into cell-specific molecular changes occurring within the ARC during DOCA-salt treatment, and prompt increased investigation of the physiological and pathophysiological significance of distinct subtypes of neuronal and glial cell types.https://www.frontiersin.org/articles/10.3389/fncel.2023.1207350/fullsnRNAseqDOCA-saltarcuate nucleusAgRP neuronsmicrogliamouse |
| spellingShingle | Valerie A. Wagner Valerie A. Wagner Guorui Deng Kristin E. Claflin McKenzie L. Ritter Huxing Cui Huxing Cui Huxing Cui Pablo Nakagawa Pablo Nakagawa Curt D. Sigmund Curt D. Sigmund Curt D. Sigmund Lisa L. Morselli Justin L. Grobe Justin L. Grobe Justin L. Grobe Justin L. Grobe Justin L. Grobe Anne E. Kwitek Anne E. Kwitek Anne E. Kwitek Anne E. Kwitek Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension Frontiers in Cellular Neuroscience snRNAseq DOCA-salt arcuate nucleus AgRP neurons microglia mouse |
| title | Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension |
| title_full | Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension |
| title_fullStr | Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension |
| title_full_unstemmed | Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension |
| title_short | Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension |
| title_sort | cell specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate salt model of hypertension |
| topic | snRNAseq DOCA-salt arcuate nucleus AgRP neurons microglia mouse |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1207350/full |
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