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Stellate cells are in utero markers of pancreatic disease in cystic fibrosis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Ovis aries

PROVIDER: GSE254376 | GEO | 2025/03/17

REPOSITORIES: GEO

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Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.

Project description:BackgroundPancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation.MethodsFetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry.ResultsTranscriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term.ConclusionThe transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

| S-EPMC11304907 | biostudies-literature

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis[RNA-seq]

Project description:Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use the sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. Transcriptomic evidence from bulk RNA-seq showed alterations in the CF pancreas by 65 days of gestation, which are accompanied by marked pathological changes by 80 days gestation. These include a profound fibrotic response, confirmed by immunostaining for COL1A1, SMA and SPARC, together with acinar destruction. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CF animals at 80- and 120-days gestation, as are activated stellate cells at term. This cellular imbalance likely has a pivotal role in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent CF pancreatic destruction.

2025-03-17 | GSE254375 | GEO

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis [scRNA-seq]

Project description:Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use the sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. Transcriptomic evidence from bulk RNA-seq showed alterations in the CF pancreas by 65 days of gestation, which are accompanied by marked pathological changes by 80 days gestation. These include a profound fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar destruction. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CF animals at 80- and 120-days gestation, as are activated stellate cells at term. This cellular imbalance likely has a pivotal role in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent CF pancreatic destruction.

2025-03-17 | GSE254374 | GEO

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis

Project description:Stellate cells are in utero markers of pancreatic disease in cystic fibrosis

| PRJNA1070269 | ENA

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis[RNA-seq]

Project description:Stellate cells are in utero markers of pancreatic disease in cystic fibrosis[RNA-seq]

| PRJNA1070273 | ENA

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis [scRNA-seq]

Project description:Stellate cells are in utero markers of pancreatic disease in cystic fibrosis [scRNA-seq]

| PRJNA1070271 | ENA

Transcriptome profile of Primary Human Lung Fibroblasts (Cystic Fibrosis vs. Non-Cystic Fibrosis)

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-15 | GSE141537 | GEO

Expression data from pancreatic stellate cells and cancer cell line MiaPaca2

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-08-09 | E-GEOD-49588 | biostudies-arrayexpress

Burkholderia cepacia complex and cystic fibrosis (CF) patients

Project description:This SuperSeries is composed of the SubSeries listed below.

2011-08-22 | GSE30568 | GEO

Cystic fibrosis causes olfactory system defects by altering progenitor cell proliferation

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-31 | GSE197187 | GEO

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