Similar Datasets
Project description:Differential lncRNA and mRNA expression in Hirschsprung's disease (HSCR)
| PRJNA935950 | ENA
Project description:The enteric nervous system (ENS) is a complex network of neurons and glial cells. Hirschsprung's disease (HSCR) is a congenital condition characterized by the absence of ganglion cells in the distal colon, leading to functional bowel obstruction. In this study, we used single-cell RNA sequencing (scRNA-seq) and whole genome sequencing (WGS) to analyze healthy and aganglionic colon segments from HSCR patients. Using scRNA-seq, we identified 13 major cell types in patient samples and observed that neural progenitor cells were present in both healthy and aganglionic colon regions, while mature neurons were absent from aganglionic colon. In these progenitor cells, critical differentiation pathway genes displayed reduced expression in the aganglionic colon, suggesting a disruption in their transition to mature neuronal cell types. Furthermore, transcriptomic analysis revealed significant alterations in gene expression across several stromal cell types. These transcriptomic shifts, particularly in mast cells, support the hypothesis that altered gene expression in the microenvironment of neural progenitor cells contributes to impaired differentiation. Our findings support the hypothesis that neural precursors in HSCR are capable of migration, but they are defective in their differentiation to mature cell types. Our analysis provides insights into potential therapeutic targets to stimulate neurogenesis in the aganglionic colon.
2025-12-31 | GSE312486 | GEO
Project description:Several microRNAs which assosiate with Hirschsprung's disease were screened from 271 differentially expressed microRNAs between pathological changed colon segments of Hirschsprung's Disease and normal colon.These identified miRNAs could be used as diagnostic markers of HSCR segments.
2016-01-28 | GSE77296 | GEO
Project description:Hirschsprung disease (HSCR) is a congenital intestinal disorder characterized by the absence of ganglia in the distal intestine. Despite surgical resection of the aganglionic intestine and pull-through surgery, HSCR patients still experience bowel dysfunction, indicating that latent abnormalities may also exist in the proximal ganglionic intestine. To elucidate possible causes of postoperative bowel dysfunction in HSCR, we investigated differences in the proximal ganglionic intestine using an animal model of HSCR (Ednrb-null mice) and validated our findings in tissue from human HSCR patients. We found that the proximal ganglionic colon of HSCR mice exhibited greater stiffness and fibrosis than their wild-type littermates. Similarly, submucosal fibrosis was significantly greater in the proximal ganglionic intestine of HSCR patients than in intestinal tissue from age and site-matched controls. Furthermore, we observed dysregulated expression of extracellular matrix (ECM)-related genes in the proximal ganglionic intestine of HSCR mice compared to controls. We conclude that increased fibrosis, stiffness, and alterations in ECM composition may contribute to persistent dysfunction of the ganglionic intestine in HSCR. These findings add to the growing body of literature that describe abnormalities in the proximal ganglionic intestine of HSCR and suggest that HSCR is not limited to the aganglionic intestine alone.
2025-12-12 | GSE305622 | GEO
Project description:Background & Aims Enteric glial cells (EGCs) play vital roles in gut homeostasis and neurogenesis. Hirschsprung disease (HSCR) is a neurocristopathy, yet paradoxically, neural crest-derived enteric glial cells (EGCs) are present within the muscle of the affected region. This study investigates the molecular identity, origins, and neurogenic potential of EGCs in the aganglionic mouse and human colon. Methods We utilized single-cell RNA sequencing (scRNA-seq) from aganglionic and ganglionated segments of 10-14 day old Ednrb-null mice (Plp1-GFP;Ednrb-/-) and wild-type controls. Results scRNA-seq revealed the absence of GFAP+ intraganglionic (IG) glia in aganglionic colon, while CAMK2b+ extraganglionic (EG) glia and Schwann-like cells (SLCs) were present. EG glia exhibited a transcriptional profile similar to SLCs, suggesting a possible shared embryonic origin. Conclusions A subpopulation of extraganglionic EGCs, transcriptionally similar to SLCs, persists in the aganglionic segment of HSCR.
2025-10-15 | GSE293138 | GEO
Project description:This dataset contains bulk RNA sequencing data from paired aganglionic and ganglionic colonic tissue specimens obtained from three pediatric patients diagnosed with Hirschsprung disease (HSCR, OMIM 142623). RNA was extracted and sequenced to investigate transcriptomic alterations and signaling pathway dysregulation associated with HSCR pathogenesis. Raw paired-end FASTQ files generated by Illumina NovaSeq 6000 sequencing are provided for each sample, enabling downstream analyses of differential gene expression between diseased and unaffected intestinal segments.
2025-08-14 | GSE305450 | GEO
Project description:Urine miRNA signature as potential non-invasive diagnostic biomarker for Hirschsprung’s Disease (HSCR): Unfortunately, HSCR diagnosis remains a challenge: current diagnostic methods are too invasive and difficult to conduct and to interpret. We designed this study in urine with the aim of identifying a non-invasive biomarker, which undoubtfully, would be a more convenient method for both babies and parents in the future.
2025-01-13 | GSE277874 | 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: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:To further development of our lncRNA and mRNA expression approach to pancreatic ductal adenocarcinoma(PDAC), we have employed lncRNA and mRNA microarray expression profiling as a discovery platform to identify lncRNA and mRNA expression in pancreatic ductal adenocarcinoma.Human pancreatic ductal adenocarcinoma tissues and normal pancreatic tissues from PDAC donors and other duodenum diseases donors. analyze mRNA and lncRNA expression in pancreatic ductal adenocarcinoma (PDAC) by microarray platform
2014-11-18 | E-GEOD-57144 | biostudies-arrayexpress