{"doi":"10.1016/j.appet.2022.106022","title":"A comparative transcriptomic analysis of glucagon-like peptide-1 receptor- and glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus","abstract":null,"journal":"Appetite","year":2022,"id":605261,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1553256,"name":"Ryan Patterson-Cross","orcid":null,"position":1,"is_corresponding":false},{"id":1026069,"name":"Orla Woodward","orcid":null,"position":2,"is_corresponding":false},{"id":1553259,"name":"Jo Lewis","orcid":null,"position":3,"is_corresponding":false},{"id":865999,"name":"Davide Chiarugi","orcid":"0000-0003-2752-3189","position":4,"is_corresponding":false},{"id":1553263,"name":"Florian Merkle","orcid":null,"position":5,"is_corresponding":false},{"id":1553265,"name":"Fiona Gribble","orcid":null,"position":6,"is_corresponding":false},{"id":260268,"name":"Frank Reimann","orcid":"0000-0001-9399-6377","position":7,"is_corresponding":false},{"id":1553267,"name":"Alice Adriaenssens","orcid":null,"position":8,"is_corresponding":false},{"id":1218263,"name":"Christopher Smith","orcid":"0000-0002-1909-9245","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A comparative transcriptomic analysis of glucagon-like peptide-1 receptor- and glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus","abstract":"The hypothalamus is a key region of the brain implicated in homeostatic regulation, and is an integral centre for the control of feeding behaviour. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones with potent glucoregulatory function through engagement of their respective cognate receptors, GLP-1R and GIPR. Recent evidence indicates that there is a synergistic effect of combining GIP- and GLP-1-based pharmacology on appetite and body weight. The mechanisms underlying the enhanced weight loss exhibited by GIPR/GLP-1R co-agonism are unknown. Gipr and Glp1r are expressed in the hypothalamus in both rodents and humans. To better understand incretin receptor-expressing cell populations, we compared the cell types and expression profiles of Gipr- and Glp1r-expressing hypothalamic cells using single-cell RNA sequencing. Using Glp1r-Cre or Gipr-Cre transgenic mouse lines, fluorescent reporters were introduced into either Glp1r- or Gipr-expressing cells, respectively, upon crossing with a ROSA26-EYFP reporter strain. From the hypothalami of these mice, fluorescent Glp1rEYFP+ or GiprEYFP+ cells were FACS-purified and sequenced using single-cell RNA sequencing. Transcriptomic analysis provided a survey of both non-neuronal and neuronal cells, and comparisons between Glp1rEYFP+ and GiprEYFP + populations were made. A total of 14,091 Glp1rEYFP+ and GiprEYFP+ cells were isolated, sequenced and taken forward for bioinformatic analysis. Both Glp1rEYFP+ and GiprEYFP+ hypothalamic populations were transcriptomically highly heterogeneous, representing vascular cell types, oligodendrocytes, astrocytes, microglia, and neurons. The majority of GiprEYFP+ cells were non-neuronal, whereas the Glp1rEYFP+ population was evenly split between neuronal and non-neuronal cell types. Both Glp1rEYFP+ and GiprEYFP+ oligodendrocytes express markers for mature, myelin-forming oligodendrocytes. While mural cells are represented in both Glp1rEYFP+ and GiprEYFP+ populations, Glp1rEYFP+ mural cells are largely smooth muscle cells, while the majority of GiprEYFP+ mural cells are pericytes. The co-expression of regional markers indicate that clusters of Glp1rEYFP+ and GiprEYFP+ neurons have been isolated from the arcuate, ventromedial, lateral, tuberal, suprachiasmatic, and premammillary nuclei of the hypothalamus. We have provided a detailed comparison of Glp1r and Gipr cells of the hypothalamus with single-cell resolution. This resource will provide mechanistic insight into how engaging Gipr- and Glp1r-expressing cells of the hypothalamus may result in changes in feeding behaviour and energy balance.","is_dataset_classified":null,"base_score":3.784189633918261,"endowment":3.784189633918261,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35430298","pmcid":"PMC7614381","openalex_id":"https://openalex.org/W4224132502","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"220271/Z/20/Z","title":null},{"funder_name":"MRC","grant_id":"MRC_MC_UU_12012/3","title":null},{"funder_name":"Wellcome Trust","grant_id":"211221/Z/18/Z","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_00014/3","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/P501967/1","title":null},{"funder_name":"Academy of Medical Sciences","grant_id":"SBF001\\1016","title":null},{"funder_name":"Wellcome Trust","grant_id":"106263/Z/14/Z","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_00014/5","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_12012/3","title":null},{"funder_name":"Wellcome Trust","grant_id":"220271","title":"Targeting the gut in metabolic disease"},{"funder_name":"New York Stem Cell Foundation","grant_id":"","title":null},{"funder_name":"AstraZeneca","grant_id":"","title":null},{"funder_name":"Eli Lilly and Company","grant_id":"","title":null},{"funder_name":"Chan Zuckerberg Initiative","grant_id":"","title":null}],"total_grants":14,"fwci":3.2683,"citation_percentile":0.93347193,"influential_citations":0,"citation_trend":[{"year":2022,"count":5},{"year":2023,"count":5},{"year":2024,"count":10},{"year":2025,"count":13},{"year":2026,"count":10}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1016/j.appet.2022.106022","host_type":"journal"},{"url":"https://doi.org/10.1016/j.appet.2022.106022","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0195666322001131?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0195666322001131?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35430298","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7614381","host_type":"repository"},{"url":"https://www.repository.cam.ac.uk/handle/1810/336383","host_type":"repository"},{"url":"https://doi.org/10.17863/cam.83800","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7614381","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7614381?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.17863/cam.83800","host_type":""},{"url":"http://dx.doi.org/10.1016/j.appet.2022.106022","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-000A-629D-7","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-000A-629F-5","host_type":""}],"fields_of_study":["Regulation of Appetite and Obesity","Diabetes Treatment and Management","Pancreatic function and diabetes","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Glucagon-Like Peptide-1 Receptor","Animals","Gastric Inhibitory Polypeptide","Glucose","Humans","Hypothalamus","Mice","Glucagon-Like Peptide 1","Incretins","Transcriptome"],"keywords":["Internal medicine","Biology","Endocrinology","Receptor","Hypothalamus","Incretin","Glucagon-like peptide-1","Population","Proglucagon","Enteroendocrine cell","Gastric inhibitory polypeptide","Cell type","Glucagon","Cell biology","Cell","Hormone","Biochemistry","Type 2 diabetes","Endocrine system","Medicine","Feeding","Appetite","Glucose-dependent Insulinotropic Polypeptide","Transcriptomics","Gut-brain Axis","Incretins","Article","Glucagon-Like Peptide-1 Receptor","Mice","Glucose","Glucagon-Like Peptide 1","Animals","Humans","Transcriptome"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T02:01:41.209567Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}