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| Status |
Public on Sep 30, 2015 |
| Title |
Illumina Human Polycystic Liver Disease and Normal Biliary Stem Cell RNAseq |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Background & aims: Polycystic liver disease (PLD) is an autosomal dominantly inherited disorder caused by mutations in genes such as PRKCSH and SEC63. It has been thought that cysts develop from biliary progenitor cells due to loss-of-heterozygosity (LOH), leading to aberrant proliferation or defects in differentiation. Cyst expansion can be suppressed by somatostatin analogues such as lanreotide. There is no human in vitro model available that truly recapitulates polycystic liver disease. We hypothesize that PLD progenitors can form bipotent liver organoids that carry key features of cyst development. To find gene expression differences between Human Polycystic Liver Disease and Normal Biliary Stem Cells.
Methods: Cells from normal biliary duct (n=6), cyst biliary epithelium (n=60) and cyst fluid (n=31) were isolated and placed under conditions suitable for expansion of human adult liver stem cells. We analyzed genetic LOH, gene expression, differentiation capacity, response to lanreotide and cilium formation of these organoids.
Results: Cholangiocytes from cyst biliary epithelium (47/60) and cyst fluid (9/31) proved capable of expanding as bipotent liver organoids. Multiple cyst organoids displayed LOH surrounding PRKCSH or SEC63 regions. Organoids formed cilia when proliferation was inhibited. Neither hepatocyte nor biliary differentiation of PLD organoids was impaired. RNAseq revealed no significantly dysregulated pathway in PLD organoids. Lanreotide significantly decreased expansion of liver organoids in comparison to negative control (197% ± 46% versus 547% ± 28%; p: 0.038).
Conclusion & discussion: Biliary progenitor cells from patient cyst epithelium and fluid can expand into liver organoids. They recapitulate key characteristics of PLD, and are a promising human in vitro model for research, diagnostics and treatment of polycystic liver diseases and cholangiociliopathies.
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| Overall design |
8 polycystic liver disease samples versus 4 control samples
RADBOUDUMC
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| |
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| Contributor(s) |
Wills ES, Drenth JP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 29, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Edgar Wills |
| E-mail(s) |
edgar.wills@gmail.com
|
| Phone |
+31617411834
|
| Organization name |
RadboudUMC
|
| Department |
Gastroenterology & Hepatology
|
| Street address |
Andrej Sacharowstraat 37
|
| City |
The Hague |
| ZIP/Postal code |
2552HK |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| GSM1898277 |
normalbiliarystemcell_expansionmedium_1 n2 |
| GSM1898278 |
normalbiliarystemcell_expansionmedium_1 n3 |
| GSM1898279 |
normalbiliarystemcell_expansionmedium_1 n4 |
| GSM1898280 |
normalbiliarystemcell_expansionmedium_1 n10 |
| GSM1898281 |
polycysticstemcell_expansionmedium_1 2p6 |
| GSM1898282 |
polycysticstemcell_expansionmedium_1 8p6 |
| GSM1898283 |
polycysticstemcell_expansionmedium_1 9p6 |
| GSM1898284 |
polycysticstemcell_expansionmedium_1 10p4 |
| GSM1898285 |
polycysticstemcell_expansionmedium_1 12p5 |
| GSM1898286 |
polycysticstemcell_expansionmedium_1 15p6 |
| GSM1898287 |
polycysticstemcell_expansionmedium_1 16p6 |
| GSM1898288 |
polycysticstemcell_expansionmedium_1 17p6 |
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| Relations |
| BioProject |
PRJNA297355 |
| SRA |
SRP064321 |
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