Gene expression-based, etiology analysis for Hirschsprung's Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE77296 | GEO | 2016/01/28
SECONDARY ACCESSION(S): PRJNA309981
REPOSITORIES: GEO
Similar Datasets
Project description:Objective Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs). Design ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single cell RNA-sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors’ capacity to integrate and restore functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility. Results We found that our protocol consistently gives rise to high yields of cell populations exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed increased basal contractile activity and increased responses to electrical stimulation compared to control tissue. Conclusion Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and restore functional responses in human HSCR patient colonic tissue.
2024-09-30 | GSE252061 | GEO
Project description:In order to determine the serum microRNAs profile from middle-old aged patients with acute ischemic stroke and investigate possible diagnostic value of these differential microRNAs.The blood samples of 117 IS patients and 82 healthy people were collected. Differential miRNAs in serum from IS and control were screened with miRNA microarray analysis, and the expression of selected miRNAs were validated by quantitative reverse-transcriptase polymerase chain reaction assays (qRT-PCR). Results: We discovered 115 differentially expressed miRNAs, among which miR-32-3p, miR-106-5p, miR-532-5p were found be related to IS for the first time. Conclusions: In the present study, we identified the changed expression pattern of miRNAs in IS. Serum miR-32-3p, miR-106-5p, miR-1246 and miR-532-5p may serve as potential diagnostic biomarkers for IS. During the initial screening stage, we divided the serum samples into five groups (10 serum samples were pooled to form a group). Group A1: A denotes thrombotic stroke and 1 denotes hepertension. Group A14: A denotes thrombotic stroke, 1 denotes hepertension and 4 denotes hyperlipidemia. Group B2: B denotes embolic stroke and 2 denotes heart disease. Group B12: B denotes embolic stroke, 1 denotes hepertension and 2 denotes heart disease. Group 0: healthy control group.
2015-08-12 | E-GEOD-60319 | biostudies-arrayexpress
Project description:To address the role of miRNAs in Hirschsprund disease (HSCR), we carried out microRNA (miRNA) array analysis by using human intestinal samples obtained from HSCR patients and controls, and identified dysregulated miRNAs involved in the pathogenesis of HSCR.
2024-05-02 | GSE200369 | GEO
Project description:In order to determine the serum microRNAs profile from middle-old aged patients with acute ischemic stroke and investigate possible diagnostic value of these differential microRNAs.The blood samples of 117 IS patients and 82 healthy people were collected. Differential miRNAs in serum from IS and control were screened with miRNA microarray analysis, and the expression of selected miRNAs were validated by quantitative reverse-transcriptase polymerase chain reaction assays (qRT-PCR). Results: We discovered 115 differentially expressed miRNAs, among which miR-32-3p, miR-106-5p, miR-532-5p were found be related to IS for the first time. Conclusions: In the present study, we identified the changed expression pattern of miRNAs in IS. Serum miR-32-3p, miR-106-5p, miR-1246 and miR-532-5p may serve as potential diagnostic biomarkers for IS.
2015-08-12 | GSE60319 | GEO
Project description:Using the highly sensitive miRCURY LNA™ microRNA array, we screened 3100 microRNAs abundant in the human colon cancer and Adjacent normal gastric mucosa tissues, and the function of differentially expressed microRNAs were analyzed by bioinformatics. The enrichment results indicated that these microRNAs perhaps participated in the occurrence and development process of colon cancer. In this study, three cases of colon cancer were used to acquire the microRNA expression profiling, and qPCR was employed to confirm the results of microRNA chip. The function of the differentially expressed microRNA were analyzed by bioinformatic methods.Finally,compared with the adjacent normal mucosa tissues，the expression of 2 microRNAs were up regulated in colon cancer. qPCR results showed an expression pattern consistent with that of the chip analysis.
2017-07-18 | GSE101502 | GEO
Project description:Purpose: Hirschsprung’s disease (HSCR, OMIM 142623) represents one of the main causes of neonatal intestinal obstruction. It is caused by dysfunction of neural crest cells (NCCs) and their progeny during development of the enteric nervous system (ENS). HSCR is considered a multifactorial disorder, however, associated risk genes only account for a minority of cases. Consequently, defining disease-relevant variants is still a demanding task. Methods: To reduce the number of candidate genes identified by Whole Exome Sequencing (WES) and to examine their disease-causing relevance, we established a complementary study pipeline including transcriptome data of murine embryonic ENS-relevant tissues, literature and database searches, in silico network analyses as well as functional assays using genome-edited candidate-specific cell clones. Results: Applying this strategy on a pilot set of two HSCR patients and their non-affected parents led to the identification of four novel HSCR candidate genes: ATP7A, SREBF1, ABCD1 and PIAS2. This candidate gene selection was corroborated by the discovery of further rare variants in additional HSCR cases. Moreover, expression analyses revealed that all four genes are expressed in embryonic murine gastrointestinal tissues. Functional analyses using candidate gene-specific, neuronal-like CRISPR/Cas9-edited knockout cell clones demonstrated impaired differentiation, proliferation and/or cell survival capacity. Conclusions: Taken together, the presented study pipeline was proven to be suitable for the selection and validation of candidate genes as well as to gain insight into underlying pathomechanisms of HSCR.
2020-10-12 | GSE144442 | GEO
Project description:Hirschsprung disease (HSCR) is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. The HSCR phenotype is highly variable with respect to gender, segment length of aganglionosis, familiality and the presence of additional anomalies. By molecular genetic analysis, a minimum of 11 neuro-developmental genes (RET, GDNF, NRTN, SOX10, EDNRB, EDN3, ECE1, ZFHX1B, PHOX2B, KIAA1279, TCF4) are known to harbor rare high-penetrance mutations that confer a large risk to the bearer. In addition, two other genes (RET, NRG1) harbor common low-penetrance polymorphisms that contribute only partially to risk and act as genetic modifiers. To broaden this search, we examined whether a set of 67 proven and candidate HSCR genes harbored additional modifier alleles. In this pilot study, we utilized a custom-designed array CGH with ~33,000 test probes at an average resolution of ~185bp to detect gene-sized or smaller copy number variants (CNVs) within these 67 genes in 18 heterogeneous HSCR patients. Using stringent criteria, we identified CNVs at three loci (MAPK10, ZFHX1B, SOX2) that are novel, involve regulatory and coding sequences of these neuro-developmental genes and show association with HSCR in combination with other congenital anomalies. Two-condition experiment: Patient vs. Control. Sex-matched controls. Technical replicates: 4 were examined twice and 3 were studied in triplicate. Technical replicates: 408.3.1, 408.3.2 Technical replicates: 300.3.1, 300.3.2 Technical replicates: 354.3.1, 354.3.2 Technical replicates: 355.3.1, 355.3.2 Technical replicates: 63.3.1, 63.3.2, 63.3.3 Technical replicates: 122.7.1, 122.7.2, 122.7.3 Technical replicates: 413.3.1, 413.3.2, 413.3.3
2011-05-06 | E-GEOD-29051 | biostudies-arrayexpress
Project description:Hirschsprung’s disease (HSCR) is a congenital disease which is characterized by the reduction or absence of neurons and glial cells in the enteric nervous system (ENS). Failure of neural crest cells (NCCs) to colonize the gut during the embryonic development has been considered as one of the possible causes of the disease. In this study, the migration and gene expression of sacral NCCs from the spontaneous mouse mutant Dominant megacolon (Dom) which is a HSCR animal model expressing a mutated transcription factor Sox10, were analyzed in order to identify candidate genes which may possibly affect the NCC migration in the mutant.
2020-11-17 | GSE161579 | GEO
Project description:Hirschsprung disease (HSCR) is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. The HSCR phenotype is highly variable with respect to gender, segment length of aganglionosis, familiality and the presence of additional anomalies. By molecular genetic analysis, a minimum of 11 neuro-developmental genes (RET, GDNF, NRTN, SOX10, EDNRB, EDN3, ECE1, ZFHX1B, PHOX2B, KIAA1279, TCF4) are known to harbor rare high-penetrance mutations that confer a large risk to the bearer. In addition, two other genes (RET, NRG1) harbor common low-penetrance polymorphisms that contribute only partially to risk and act as genetic modifiers. To broaden this search, we examined whether a set of 67 proven and candidate HSCR genes harbored additional modifier alleles. In this pilot study, we utilized a custom-designed array CGH with ~33,000 test probes at an average resolution of ~185bp to detect gene-sized or smaller copy number variants (CNVs) within these 67 genes in 18 heterogeneous HSCR patients. Using stringent criteria, we identified CNVs at three loci (MAPK10, ZFHX1B, SOX2) that are novel, involve regulatory and coding sequences of these neuro-developmental genes and show association with HSCR in combination with other congenital anomalies.
2011-05-06 | GSE29051 | GEO