PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA310148 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3129210.fastq.gz | Fastqsanger.gz | |||
| SRR3129220.fastq.gz | Fastqsanger.gz | |||
| SRR3129211.fastq.gz | Fastqsanger.gz | |||
| SRR3129221.fastq.gz | Fastqsanger.gz | |||
| SRR3129212.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
2016-07-11 | GSE77302 | GEO
Project description:Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
2016-07-11 | GSE77357 | GEO
Project description:PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells [ChIP-Seq]
| PRJNA309997 | ENA
Project description:PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells [RNA-Seq]
| PRJNA310130 | ENA
Project description:Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome-wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
| S-EPMC4940164 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-07-11 | GSE77367 | GEO
Project description:Dietary vitamin A is metabolized into bioactive retinoic acid in vivo and regulates the development of many embryonic tissues. Retinoic acid signaling is active in the oral ectoderm-derived tissues of the neuroendocrine system, but its role there has not yet been fully explored. We show here that retinoic acid signaling is active during pituitary organogenesis and dependent on the pituitary transcription factor Prop1. Prop1-mutant mice show reduced expression of the aldehyde dehydrogenase gene Aldh1a2, which metabolizes the vitamin A-intermediate retinaldehyde into retinoic acid. In order to elucidate the specific function of RA signaling during neuroendocrine development, we studied a conditional deletion of Aldh1a2 and a dominant-negative mouse model of inhibited retinoic acid signaling during pituitary organogenesis. These models partially phenocopy Prop1-mutant mice by exhibiting embryonic pituitary dysmorphology and reduced hormone expression, especially of thyroid-stimulating hormone. These findings establish the critical role of retinoic acid in embryonic pituitary stem cell progression to differentiated hormone cells and raise the question of gene-by-environment interactions as contributors to pituitary development and disease.
2020-02-26 | GSE142074 | GEO
Project description:Mutations in the pituitary specific transcription factor Prophet of Pit-1 (PROP1) are the most common genetic etiology of combined pituitary hormone deficiency (CPHD). CPHD is associated with short stature, attributable to growth hormone deficiency and/or thyroid stimulating hormone deficiency, as well as hypothyroidism and infertility. Pathogenic lesions impair pituitary development and differentiation of endocrine cells. We performed single-cell RNA sequencing of pituitary cells from a wild-type and a Prop1-mutant P4 female to elucidate population-specific differential gene expression. We observed a Smoc2+ve population that expressed low Sox2, which trajectory analyses suggest are a transitional cell state as stem cells differentiate into endocrine cells. We also detected ectopic expression of Sox21 in these cells in the Prop1df/df mutant. Prop1-mutant mice are known to overexpress Pou3f4, which we now show to be also enriched in this Smoc2+ve population. We sought to elucidate the role of Pou3f4 during pituitary development and to determine the contributions of Pou3f4 upregulation to pituitary disease by utilizing double-mutant mice lacking both Prop1 and Pou3f4. However, our data showed that Pou3f4 is not required for normal pituitary development and function. Double mutants further demonstrated that the upregulation of Pou3f4 was not causative for the overexpression of Sox21. These data indicate loss of Pou3f4 is not a potential cause of CPHD, and further studies may investigate the functional consequence of upregulation of Pou3f4 and Sox21, if any, in the novel Smoc2+ve cell population.
2024-08-03 | GSE273683 | GEO
Project description:The pituitary gland exhibits sex differences in its function. Diseases associated with dysregulation of the pituitary are also sex-biased in prevalence. Previous qPCR profiling of puberty-related genes in the pituitary gland revealed increasingly sex-biased expression of genes profiled across pubertal transition. Here, we performed small RNA-seq on total RNA extracted from C57BL/6J mouse pituitary gland of both sexes mice at 4 ages spanning pubertal transition (postnatal days 12, 22, 27, 32) (6 replicates per sex at each age) to examine microRNA (miRNA) regulation of sex differences in gene expression observed. Total RNA was sent to SickKids TCAG core to construct small RNA-seq libraries using NEBNext Small RNA Library Prep Kit according to manufacterer’s protocol. Resulting single-end libraries were sequenced at TCAG core on the Illumina HiSeq 2500 v4 flow cell with SR50 bp. Data obtained was processed using miRDeep2 pipeline to align small RNA-seq reads to the mouse genome (mm10) and to filter for miRNAs.
2022-10-12 | E-MTAB-9460 | biostudies-arrayexpress
Project description:The pituitary gland exhibits sex differences in its function. Diseases associated with dysregulation of the pituitary are also sex-biased in prevalence. Previous qPCR profiling of puberty-related genes in the pituitary gland revealed increasingly sex-biased expression of genes profiled across pubertal transition. Here, we performed 3’-UTR-seq on pituitary gland from both sexes of C57BL/6J mice at 5 ages spanning pubertal transition (postnatal days 12, 22, 27, 32, 37) (6 replicates per sex at each age) to examine genome-wide sex-biased trends in gene expression and potential regulatory mechanisms of these sex differences. QuantSeq 3’mRNA-seq libraries were constructed from total RNA using an automated method with Agilent NGS Workstation. Resulting single-end libraries were sequenced at SickKids TCAG core on the Illumina v4 flow cell with SR50 bp cycles extended to 68 bp. A customized pipeline was developed and used for analysis of reads obtained (see paper for details). Processed reads were mapped to mouse genome (mm10).
2022-10-12 | E-MTAB-9459 | biostudies-arrayexpress