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Article ; Online: Male rat hypothalamic extraretinal photoreceptor Opsin3 is sensitive to osmotic stimuli and light.

Bárez-López, Soledad / Bishop, Paul / Searby, Daniel / Murphy, David / Greenwood, Michael P

2024 Volume 36, Issue 2, Page(s) e13363

Abstract: The light-sensitive protein Opsin 3 (Opn3) is present throughout the mammalian brain; however, the role of Opn3 in this organ remains unknown. Since Opn3 encoded mRNA is modulated in the supraoptic and paraventricular nucleus of the hypothalamus in ... ...

Abstract	The light-sensitive protein Opsin 3 (Opn3) is present throughout the mammalian brain; however, the role of Opn3 in this organ remains unknown. Since Opn3 encoded mRNA is modulated in the supraoptic and paraventricular nucleus of the hypothalamus in response to osmotic stimuli, we have explored by in situ hybridization the expression of Opn3 in these nuclei. We have demonstrated that Opn3 is present in the male rat magnocellular neurones expressing either the arginine vasopressin or oxytocin neuropeptides and that Opn3 increases in both neuronal types in response to osmotic stimuli, suggesting that Opn3 functions in both cell types and that it might be involved in regulating water balance. Using rat hypothalamic organotypic cultures, we have demonstrated that the hypothalamus is sensitive to light and that the observed light sensitivity is mediated, at least in part, by Opn3. The data suggests that hypothalamic Opn3 can mediate a light-sensitive role to regulate circadian homeostatic processes.
MeSH term(s)	Animals ; Male ; Rats ; Arginine Vasopressin/metabolism ; Hypothalamus/metabolism ; In Situ Hybridization ; Mammals ; Oxytocin/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; Vasopressins/metabolism
Chemical Substances	Arginine Vasopressin (113-79-1) ; Oxytocin (50-56-6) ; Vasopressins (11000-17-2)
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.13363
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Zs.A 2634: Show issues

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Article ; Online: Isoflurane Rapidly Modifies Synaptic and Cytoskeletal Phosphoproteomes of the Supraoptic Nucleus of the Hypothalamus and the Cortex.

Bárez-López, Soledad / Gadd, George J / Pauža, Audrys G / Murphy, David / Greenwood, Michael P

Neuroendocrinology

2023 Volume 113, Issue 10, Page(s) 1008–1023

Abstract: Introduction: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the ... ...

Abstract	Introduction: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia (GA) and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of GA. In order to identify potential phosphorylation events in the brain-mediating GA effects, we have explored the phosphoproteome responses in the rat SON and compared these to cingulate cortex (CC) which displays no FOS activation in response to general anaesthetics. Methods: Adult Sprague-Dawley rats were treated with isoflurane for 15 min. Proteins from the CC and SON were extracted and processed for nano-LC mass spectrometry (LC-MS/MS). Phosphoproteomic determinations were performed by LC-MS/MS. Results: We found many changes in the phosphoproteomes of both the CC and SON in response to 15 min of isoflurane exposure. Pathway analysis indicated that proteins undergoing phosphorylation adaptations are involved in cytoskeleton remodelling and synaptic signalling events. Importantly, changes in protein phosphorylation appeared to be brain region specific suggesting that differential phosphorylation adaptations might underlie the different neuronal activity responses to GA between the CC and SON. Conclusion: In summary, these data suggest that rapid posttranslational modifications in proteins involved in cytoskeleton remodelling and synaptic signalling events might mediate the central mechanisms mediating GA.
MeSH term(s)	Rats ; Animals ; Supraoptic Nucleus/metabolism ; Isoflurane/pharmacology ; Isoflurane/metabolism ; Chromatography, Liquid ; Rats, Sprague-Dawley ; Proto-Oncogene Proteins c-fos/metabolism ; Tandem Mass Spectrometry ; Hypothalamus/metabolism ; Anesthetics, General/metabolism ; Anesthetics, General/pharmacology ; Paraventricular Hypothalamic Nucleus/metabolism
Chemical Substances	Isoflurane (CYS9AKD70P) ; Proto-Oncogene Proteins c-fos ; Anesthetics, General
Language	English
Publishing date	2023-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000531352
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Article ; Online: Osmoadaptive GLP-1R signalling in hypothalamic neurones inhibits antidiuretic hormone synthesis and release.

Greenwood, Michael P / Greenwood, Mingkwan / Bárez-López, Soledad / Hawkins, Joe W / Short, Katherine / Tatovic, Danijela / Murphy, David

Molecular metabolism

2023 Volume 70, Page(s) 101692

Abstract: Objectives: The excessive release of the antidiuretic hormone vasopressin is implicated in many diseases including cardiovascular disease, diabetes, obesity, and metabolic syndrome. Once thought to be elevated as a consequence of diseases, data now ... ...

Abstract	Objectives: The excessive release of the antidiuretic hormone vasopressin is implicated in many diseases including cardiovascular disease, diabetes, obesity, and metabolic syndrome. Once thought to be elevated as a consequence of diseases, data now supports a more causative role. We have previously identified CREB3L1 as a transcription factor that co-ordinates vasopressin synthesis and release in the hypothalamus. The objective here was to identify mechanisms orchestrated by CREB3L1 that co-ordinate vasopressin release. Methods: We mined Creb3l1 knockdown SON RNA-seq data to identify downstream target genes. We proceeded to investigate the expression of these genes and associated pathways in the supraoptic nucleus of the hypothalamus in response to physiological and pharmacological stimulation. We used viruses to selectively knockdown gene expression in the supraoptic nucleus and assessed physiological and metabolic parameters. We adopted a phosphoproteomics strategy to investigate mechanisms that facilitate hormone release by the pituitary gland. Results: We discovered glucagon like peptide 1 receptor (Glp1r) as a downstream target gene and found increased expression in stimulated vasopressin neurones. Selective knockdown of supraoptic nucleus Glp1rs resulted in decreased food intake and body weight. Treatment with GLP-1R agonist liraglutide decreased vasopressin synthesis and release. Quantitative phosphoproteomics of the pituitary neurointermediate lobe revealed that liraglutide initiates hyperphosphorylation of presynapse active zone proteins that control vasopressin exocytosis. Conclusion: In summary, we show that GLP-1R signalling inhibits the vasopressin system. Our data advises that hydration status may influence the pharmacodynamics of GLP-1R agonists so should be considered in current therapeutic strategies.
MeSH term(s)	Liraglutide/pharmacology ; Hypothalamus/metabolism ; Neurons/metabolism ; Vasopressins/genetics ; Vasopressins/metabolism
Chemical Substances	Liraglutide (839I73S42A) ; Vasopressins (11000-17-2)
Language	English
Publishing date	2023-02-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2023.101692
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Article ; Online: Translational and Posttranslational Dynamics in a Model Peptidergic System.

Bárez-López, Soledad / Mecawi, André S / Bryan, Natasha / Pauža, Audrys G / Duque, Victor J / Gillard, Benjamin T / Murphy, David / Greenwood, Michael P

Molecular & cellular proteomics : MCP

2023 Volume 22, Issue 5, Page(s) 100544

Abstract: The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus, whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical ... ...

Abstract	The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus, whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses to neuronal stimulation are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganization of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and are hyperphosphorylated following stimulation. By multiomic integration of transcriptome and proteomic data, we identify changes to proteins present in afferent inputs to this nucleus.
MeSH term(s)	Proteome/metabolism ; Proteomics ; Hypothalamus/metabolism ; Neurons/metabolism ; Supraoptic Nucleus/metabolism
Chemical Substances	Proteome
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2075924-1
ISSN	1535-9484 ; 1535-9476
ISSN (online)	1535-9484
ISSN	1535-9476
DOI	10.1016/j.mcpro.2023.100544
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Article ; Online: Mobilisation of jerboa kidney gene networks during dehydration and opportunistic rehydration.

Gillard, Benjamin T / Amor, Nabil / Iraizoz, Fernando Alvira / Pauža, Audrys G / Campbell, Colin / Greenwood, Michael P / Alagaili, Abdulaziz N / Murphy, David

iScience

2023 Volume 26, Issue 9, Page(s) 107574

Abstract: Desert animals have evolved systems that enable them to thrive under dry conditions. Focusing on the kidney, we have investigated the transcriptomic adaptations that enable a desert rodent, the Lesser Egyptian Jerboa ( ...

Abstract	Desert animals have evolved systems that enable them to thrive under dry conditions. Focusing on the kidney, we have investigated the transcriptomic adaptations that enable a desert rodent, the Lesser Egyptian Jerboa (
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107574
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Article ; Online: Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells.

Greenwood, Mingkwan / Gillard, Benjamin T / Farrukh, Rizwan / Paterson, Alex / Althammer, Ferdinand / Grinevich, Valery / Murphy, David / Greenwood, Michael P

Molecular metabolism

2022 Volume 63, Page(s) 101542

Abstract: Objectives: Dynamic changes to neuropeptide hormone synthesis and secretion by hypothalamic neuroendocrine cells is essential to ensure metabolic homeostasis. The specialised molecular mechanisms that allow neuroendocrine cells to synthesise and secrete ...

Abstract	Objectives: Dynamic changes to neuropeptide hormone synthesis and secretion by hypothalamic neuroendocrine cells is essential to ensure metabolic homeostasis. The specialised molecular mechanisms that allow neuroendocrine cells to synthesise and secrete vast quantities of neuropeptides remain ill defined. The objective of this study was to identify novel genes and pathways controlled by transcription factor and endoplasmic reticulum stress sensor Creb3l1 which is robustly activated in hypothalamic magnocellular neurones in response to increased demand for protein synthesis. Methods: We adopted a multiomic strategy to investigate specific roles of Creb3l1 in rat magnocellular neurones. We first performed chromatin immunoprecipitation followed by genome sequencing (ChIP-seq) to identify Creb3l1 genomic targets and then integrated this data with RNA sequencing data from physiologically stimulated and Creb3l1 knockdown magnocellular neurones. Results: The data converged on Creb3l1 targets that code for ribosomal proteins and endoplasmic reticulum proteins crucial for the maintenance of cellular proteostasis. We validated genes that compose the PERK arm of the unfolded protein response pathway including Eif2ak3, Eif2s1, Atf4 and Ddit3 as direct Creb3l1 targets. Importantly, knockdown of Creb3l1 in the hypothalamus led to a dramatic depletion in neuropeptide synthesis and secretion. The physiological outcomes from studies of paraventricular and supraoptic nuclei Creb3l1 knockdown animals were changes to food and water consumption. Conclusion: Collectively, our data identify Creb3l1 as a comprehensive controller of the PERK signalling pathway in magnocellular neurones in response to physiological stimulation. The broad regulation of neuropeptide synthesis and secretion by Creb3l1 presents a new therapeutic strategy for metabolic diseases.
MeSH term(s)	Animals ; Gene Expression Regulation ; Neuroendocrine Cells ; Proteostasis ; Rats ; Rats, Sprague-Dawley ; Supraoptic Nucleus/metabolism
Language	English
Publishing date	2022-07-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2022.101542
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Article ; Online: Transcriptional and Post-Transcriptional Regulation of Oxytocin and Vasopressin Gene Expression by CREB3L1 and CAPRIN2.

Bárez-López, Soledad / Konopacka, Agnieszka / Cross, Stephen J / Greenwood, Mingkwan / Skarveli, Marina / Murphy, David / Greenwood, Michael P

Neuroendocrinology

2022 Volume 112, Issue 11, Page(s) 1058–1077

Abstract: Introduction: Water homoeostasis is achieved by secretion of the peptide hormones arginine vasopressin (AVP) and oxytocin (OXT) that are synthesized by separate populations of magnocellular neurones (MCNs) in the supraoptic and paraventricular (PVN) ... ...

Abstract	Introduction: Water homoeostasis is achieved by secretion of the peptide hormones arginine vasopressin (AVP) and oxytocin (OXT) that are synthesized by separate populations of magnocellular neurones (MCNs) in the supraoptic and paraventricular (PVN) nuclei of the hypothalamus. To further understand the molecular mechanisms that facilitate biosynthesis of AVP and OXT by MCNs, we have explored the spatiotemporal dynamic, both mRNA and protein expression, of two genes identified by our group as being important components of the osmotic defence response: Caprin2 and Creb3l1. Methods: By RNA in situ hybridization and immunohistochemistry, we have characterized the expression of Caprin2 and Creb3l1 in MCNs in the basal state, in response to dehydration, and during rehydration in the rat. Results: We found that Caprin2 and Creb3l1 are expressed in AVP and OXT MCNs and in response to dehydration expression increases in both MCN populations. Protein levels mirror the increase in transcript levels for both CREB3L1 and CAPRIN2. In view of increased CREB3L1 and CAPRIN2 expression in OXT neurones by dehydration, we explored OXT-specific functions for these genes. By luciferase assays, we demonstrate that CREB3L1 may be a transcription factor regulating Oxt gene expression. By RNA immunoprecipitation assays and Northern blot analysis of Oxt mRNA poly(A) tails, we have found that CAPRIN2 binds to Oxt mRNA and regulates its poly(A) tail length. Moreover, in response to dehydration, Caprin2 mRNA is subjected to nuclear retention, possibly to regulate Caprin2 mRNA availability in the cytoplasm. Conclusion: The exploration of the spatiotemporal dynamics of Creb3l1- and Caprin2-encoded mRNAs and proteins has provided novel insights beyond the AVP-ergic system, revealing novel OXT-ergic system roles of these genes in the osmotic defence response.
MeSH term(s)	Animals ; Rats ; Arginine Vasopressin/genetics ; Arginine Vasopressin/metabolism ; Dehydration/metabolism ; Gene Expression ; Gene Expression Regulation ; Oxytocin/genetics ; Oxytocin/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; RNA, Messenger/metabolism ; Supraoptic Nucleus/metabolism ; Water/metabolism ; Cyclic AMP Response Element-Binding Protein/genetics ; RNA-Binding Proteins/genetics
Chemical Substances	Arginine Vasopressin (113-79-1) ; Oxytocin (50-56-6) ; RNA, Messenger ; Water (059QF0KO0R) ; CREB3L1 protein, rat ; Caprin2 protein, rat ; Cyclic AMP Response Element-Binding Protein ; RNA-Binding Proteins
Language	English
Publishing date	2022-01-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000522088
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Article ; Online: Harnessing tissue-specific genetic variation to dissect putative causal pathways between body mass index and cardiometabolic phenotypes.

Leyden, Genevieve M / Shapland, Chin Yang / Davey Smith, George / Sanderson, Eleanor / Greenwood, Michael P / Murphy, David / Richardson, Tom G

American journal of human genetics

2022 Volume 109, Issue 2, Page(s) 240–252

Abstract: Body mass index (BMI) is a complex disease risk factor known to be influenced by genes acting via both metabolic pathways and appetite regulation. In this study, we aimed to gain insight into the phenotypic consequences of BMI-associated genetic variants, ...

Abstract	Body mass index (BMI) is a complex disease risk factor known to be influenced by genes acting via both metabolic pathways and appetite regulation. In this study, we aimed to gain insight into the phenotypic consequences of BMI-associated genetic variants, which may be mediated by their expression in different tissues. First, we harnessed meta-analyzed gene expression datasets derived from subcutaneous adipose (n = 1257) and brain (n = 1194) tissue to identify 86 and 140 loci, respectively, which provided evidence of genetic colocalization with BMI. These two sets of tissue-partitioned loci had differential effects with respect to waist-to-hip ratio, suggesting that the way they influence fat distribution might vary despite their having very similar average magnitudes of effect on BMI itself (adipose = 0.0148 and brain = 0.0149 standard deviation change in BMI per effect allele). For instance, BMI-associated variants colocalized with TBX15 expression in adipose tissue (posterior probability [PPA] = 0.97), but not when we used TBX15 expression data derived from brain tissue (PPA = 0.04) This gene putatively influences BMI via its role in skeletal development. Conversely, there were loci where BMI-associated variants provided evidence of colocalization with gene expression in brain tissue (e.g., NEGR1, PPA = 0.93), but not when we used data derived from adipose tissue, suggesting that these genes might be more likely to influence BMI via energy balance. Leveraging these tissue-partitioned variant sets through a multivariable Mendelian randomization framework provided strong evidence that the brain-tissue-derived variants are predominantly responsible for driving the genetically predicted effects of BMI on cardiovascular-disease endpoints (e.g., coronary artery disease: odds ratio = 1.05, 95% confidence interval = 1.04-1.07, p = 4.67 × 10
MeSH term(s)	Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Body Mass Index ; Brain/metabolism ; Brain/pathology ; Cell Adhesion Molecules, Neuronal/genetics ; Cell Adhesion Molecules, Neuronal/metabolism ; Coronary Artery Disease/genetics ; Coronary Artery Disease/metabolism ; Coronary Artery Disease/pathology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; GPI-Linked Proteins/genetics ; GPI-Linked Proteins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic Loci ; Genetic Variation ; Genome, Human ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Metabolic Networks and Pathways/genetics ; Obesity/genetics ; Obesity/metabolism ; Obesity/pathology ; Stroke Volume/physiology ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism ; Waist-Hip Ratio
Chemical Substances	Cell Adhesion Molecules, Neuronal ; GPI-Linked Proteins ; NEGR1 protein, human ; T-Box Domain Proteins ; TBX15 protein, human
Language	English
Publishing date	2022-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2021.12.013
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Article ; Online: Ageing restructures the transcriptome of the hypothalamic supraoptic nucleus and alters the response to dehydration.

Elsamad, Ghadir / Mecawi, André Souza / Pauža, Audrys G / Gillard, Benjamin / Paterson, Alex / Duque, Victor J / Šarenac, Olivera / Žigon, Nina Japundžić / Greenwood, Mingkwan / Greenwood, Michael P / Murphy, David

npj aging

2023 Volume 9, Issue 1, Page(s) 12

Abstract: Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus, which makes the antidiuretic hormone vasopressin, ageing alters acute responses to hyperosmotic cues, rendering the elderly more susceptible ...

Abstract	Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus, which makes the antidiuretic hormone vasopressin, ageing alters acute responses to hyperosmotic cues, rendering the elderly more susceptible to dehydration. Chronically, vasopressin has been associated with numerous diseases of old age, including type 2 diabetes and metabolic syndrome. Bulk RNAseq transcriptome analysis has been used to catalogue the polyadenylated supraoptic nucleus transcriptomes of adult (3 months) and aged (18 months) rats in basal euhydrated and stimulated dehydrated conditions. Gene ontology and Weighted Correlation Network Analysis revealed that ageing is associated with alterations in the expression of extracellular matrix genes. Interestingly, whilst the transcriptomic response to dehydration is overall blunted in aged animals compared to adults, there is a specific enrichment of differentially expressed genes related to neurodegenerative processes in the aged cohort, suggesting that dehydration itself may provoke degenerative consequences in aged rats.
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article
ISSN	2731-6068
ISSN (online)	2731-6068
DOI	10.1038/s41514-023-00108-2
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Article ; Online: Exome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma Formation in Crohn Disease.

Harris, R Alan / Bush, Allyson H / Eagar, Todd N / Qian, Justin / Greenwood, Michael P / Opekun, Antone R / Baldassano, Robert / Guthery, Stephen L / Noe, Joshua D / Otley, Anthony / Rosh, Joel R / Kugathasan, Subra / Kellermayer, Richard

Journal of pediatric gastroenterology and nutrition

2023 Volume 77, Issue 3, Page(s) 354–357

Abstract: Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 ... ...

Abstract	Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used to predict deleteriousness of SNPs. Human leukocyte antigen (HLA) haplotype findings were compared to a control group (n = 8496). PLINK-based analysis between GCD and NGCD groups did not find consistently significant hits. gnomAD control comparisons, however, showed consistent subgroup associations with DGKZ , ESRRA , and GXYLT1 , genes that have been implicated in mammalian granulomatous inflammation. Our findings may guide future research and precision medicine.
MeSH term(s)	Child ; Humans ; Crohn Disease/complications ; Exome Sequencing ; Genetic Predisposition to Disease ; Granuloma/genetics ; Granuloma/pathology ; Phenotype ; ERRalpha Estrogen-Related Receptor
Chemical Substances	GXYLT1 protein, human (EC 2.4.2.n2) ; DGKZ protein, human (EC 2.7.1.107)
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000003873
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