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Cyclic stretching stimuli promotes HGF and MMP secretion from hESC-derived hepatoblasts and endothelial cells towards liver lobule formation in vitro.

ABSTRACT: Cyclic stretching stimuli promotes HGF and MMP secretion from hESC-derived hepatoblasts and endothelial cells towards liver lobule formation in vitro.

PROVIDER: PRJNA970861 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24489343.fastq.gz	Fastqsanger.gz
	SRR24489344.fastq.gz	Fastqsanger.gz
	SRR24489345.fastq.gz	Fastqsanger.gz
	SRR24489346.fastq.gz	Fastqsanger.gz
	SRR24489347.fastq.gz	Fastqsanger.gz

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Cyclic stretching stimuli promotes HGF and MMP secretion from hESC-derived hepatoblasts and endothelial cells towards liver lobule formation in vitro.

Project description:We induced hepatic and endothelial cells simultaneously for day9. We applied cyclic mechancial stimuli (cMS) from day9 to day12. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells at two time points.

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Project description:The homeobox transcription factor Prox1 is expressed in embryonic hepatoblasts and remains expressed in adult hepatocytes. Prox1-null mice show severe deficiencies of liver development, but the underlying mechanisms are unknown. We studied the effects of Prox1 on the transcriptional profile of embryonic day-14 (ED14) met-murine-hepatocytes (ED14-MMH). These immortalized murine hepatoblasts express numerous hepatoblast markers, but not Prox1. We performed stable transfection with Prox1 cDNA, analyzed the transcriptome with Agilent mouse whole genome microarrays and validated genes by qRT-PCR. We observed more than 12-fold up-regulation of 22 genes and down-regulation of 232 genes. Numerous of these genes are involved in metabolic hepatocyte functions and may be regulated by Prox1 directly or indirectly, e.g. by down-regulation of HNF4a. Prox1 induces down-regulation of transcription factors, which are highly expressed in neighboring endodermal organs, suggesting a function during hepatoblast commitment. Prox1 does not influence proliferative activity of MMH but regulates genes involved in liver morphogenesis. We observed up-regulation of both type-IVa3 procollagen and functionally active matrix metalloproteinase-2 (MMP-2), which places Prox1 in the centre of liver matrix turnover. This is consistent with MMP-2 expression in hepatoblasts during liver development, and persistence of a basal lamina around the liver bud in Prox1-deficient mice. Our studies suggest that Prox1 is a multifunctional regulator of liver morphogenesis, hepatocyte function and commitment. Keywords: Met murine hepatocytes - Hex - HNF4a - MMP-2 - Type-IV collagen Keywords: Met murine hepatocytes - Hex - HNF4a - MMP-2 - Type-IV collagen

2007-05-25 | GSE7867 | GEO

Transcription profiling of mouse hepatoblasts

Project description:The homeobox transcription factor Prox1 is expressed in embryonic hepatoblasts and remains expressed in adult hepatocytes. Prox1-null mice show severe deficiencies of liver development, but the underlying mechanisms are unknown. We studied the effects of Prox1 on the transcriptional profile of embryonic day-14 (ED14) met-murine-hepatocytes (ED14-MMH). These immortalized murine hepatoblasts express numerous hepatoblast markers, but not Prox1. We performed stable transfection with Prox1 cDNA, analyzed the transcriptome with Agilent mouse whole genome microarrays and validated genes by qRT-PCR. We observed more than 12-fold up-regulation of 22 genes and down-regulation of 232 genes. Numerous of these genes are involved in metabolic hepatocyte functions and may be regulated by Prox1 directly or indirectly, e.g. by down-regulation of HNF4a. Prox1 induces down-regulation of transcription factors, which are highly expressed in neighboring endodermal organs, suggesting a function during hepatoblast commitment. Prox1 does not influence proliferative activity of MMH but regulates genes involved in liver morphogenesis. We observed up-regulation of both type-IVa3 procollagen and functionally active matrix metalloproteinase-2 (MMP-2), which places Prox1 in the centre of liver matrix turnover. This is consistent with MMP-2 expression in hepatoblasts during liver development, and persistence of a basal lamina around the liver bud in Prox1-deficient mice. Our studies suggest that Prox1 is a multifunctional regulator of liver morphogenesis, hepatocyte function and commitment. Experiment Overall Design: - two samples Experiment Overall Design: - Dye Swap design with 6 arrays

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Stretching inhibits tumor growth in MMTV-PYMT via a direct mechanical effect

Project description:Background: Tumor-associated architecture and emerging mechanical properties (forces, pressure, tension, stiffness) affect the growth and invasiveness of cancer cells. Collagen fibers aligned perpendicular to the boundaries of tumors promote local tumor invasiveness in mouse mammary tumor models and are associated with a poor prognosis in human breast cancer. Our previous study revealed that daily gentle stretching (~25% strain) for 10 min reduced the growth of P53/PTEN-/- orthotopic mouse mammary tumors by 50%. Results: In this study, we further investigated the mechanism of stretching in a more aggressive MMTV-PYMT (mammary tumor virus- polyomavirus middle T antigen) tumor model in vivo and in vitro and analyzed its impact on collagen reorganization at both the tumor-stromal interface and the tumor microenvironment composition at single cell level. Stretching reduced the average tumor size by 30–50% in orthotopic (Active and Passive Stretch) and transgenic (Passive Stretch) models. In the orthotopic model, the ratio of parallel vs. perpendicular collagen fibers relative to the tumor boundary, was greater in the Stretch group compared with the No Stretch group. Finally, stretching reduced the cell migration of collagen-embedded tumor spheroids in vitro. Conclusions: These results show that short-duration, moderate-amplitude stretching reduces tumor growth in several different animal models. We also provide evidence that this beneficial effect may be a direct mechanical effect on local matrix properties and tumor cell invasiveness

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