Comparison of RNA sequencing profiles in domed and flat colonies of ocular surface epithelial stem cells induced from human pluripotent stem cell
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157678 | GEO | 2022/01/10
REPOSITORIES: GEO
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Project description:Comparison of RNA sequencing profiles in domed and flat colonies of ocular surface epithelial stem cells induced from human pluripotent stem cell
| PRJNA662372 | ENA
Project description:The role of topographic cues in controlling commitment of induced pluripotent stem cells (iPSCs) is largely unknown. Here we demonstrate that groove-ridge nanostructures induce the elongation of iPSC colonies, guide the orientation of apical actin fibers and direct the polarity of cell division. Elongation of iPSC colonies impacts also on the intrinsic molecular patterning which seems to be orchestrated starting from the rim of the colonies. We followed the hypothesis that nanotopography directly modulates the transcriptional program of iPSC, further to guiding the overall spatial organization of the colonies. Single iPSC were seeded on flat (PI flat) and nanostructured polyimide (PI 650) and gene expression profiles were analyzed after three days. No significant differences were observed when cells were kept under culture conditions that sustained pluripotency. Then, we analyzed gene expression changes upon two weeks of multi-lineage differentiation. Many genes revealed significant expression changes in the course of differentiation and this was more pronounced on PI flat as compared to PI 650. Comparison of iPSC that were either differentiated on flat or nanostructured biomaterials revealed differential expression of several genes. Noteworthy, among significantly regulated genes, the biggest fold change on PI 650 versus PI flat after differentiation was observed in ANKRD1, which is one of the best readouts of YAP/TAZ activity. Our study suggests that nanotopography impacts on orientation and organization of iPSC colonies and highlight a possible interaction between mechanosensors and mechanotransducers.
2017-09-18 | GSE84848 | GEO
Project description:The vestibular sensory epithelium may degenerate into a layer of flat cells, known as flat epithelium, after a severe lesion, but the pathogenesis of vestibular flat epithelium remains unclear. We used microarrays to detail the global programme of gene expression in normal utricle and vestibular flat epithelium and identified whether epithelial-mesenchymal transition participite in this process
2021-09-30 | GSE179063 | GEO
Project description:Background & aim: Flat adenomas form a specific phenotype of colorectal adenomas that has been associated with more severe molecular changes and consequently a more aggressive clinical behavior compared to their polypoid counterparts. In the present study we set out to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Methods: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high resolution arrayCGH platform as well as for mutations in the adenomatous polyposis coli (APC) gene. Gene ontology on the genes located on the significantly different regions was performed. Results: Overall, flat adenomas show similar DNA copy number changes as polypoid adenomas. Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequently loss of 5q14.3 and 5q15-q23.3 in flat adenomas, while loss of 1p36.32-p35.3, 10q25.2-q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas. The 5q15-q23.3 region harbors the APC locus, therefore mutation status of APC was investigated, showing significantly less mutations in flat adenomas. Pathway analysis and datamining linked the 5q region to inflammation. Conclusion: These results provide evidence that flat and polypoid adenomas have partly overlapping DNA copy number changes, while alterations more specific to flat adenomas have associations with inflammation. Loss of 5q has been associated with aggressive behavior and this could serve as an explanation for a more aggressive clinical behavior of flat lesions.
2012-10-04 | GSE30479 | GEO
Project description:Background & aim: Flat adenomas form a specific phenotype of colorectal adenomas that has been associated with more severe molecular changes and consequently a more aggressive clinical behavior compared to their polypoid counterparts. In the present study we set out to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Methods: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high resolution arrayCGH platform as well as for mutations in the adenomatous polyposis coli (APC) gene. Gene ontology on the genes located on the significantly different regions was performed. Results: Overall, flat adenomas show similar DNA copy number changes as polypoid adenomas. Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequently loss of 5q14.3 and 5q15-q23.3 in flat adenomas, while loss of 1p36.32-p35.3, 10q25.2-q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas. The 5q15-q23.3 region harbors the APC locus, therefore mutation status of APC was investigated, showing significantly less mutations in flat adenomas. Pathway analysis and datamining linked the 5q region to inflammation. Conclusion: These results provide evidence that flat and polypoid adenomas have partly overlapping DNA copy number changes, while alterations more specific to flat adenomas have associations with inflammation. Loss of 5q has been associated with aggressive behavior and this could serve as an explanation for a more aggressive clinical behavior of flat lesions. FFPE colorectal tissue samples of 35 polypoid adenomas and 83 flat adenomas. Test samples were compared to an external pool of normal male/female reference DNA.
2012-10-04 | E-GEOD-30479 | biostudies-arrayexpress
Project description:Colonies of induced pluripotent stem cells (iPSCs) reveal aspects of self-organization even under culture conditions that maintain pluripotent state. To investigate the dynamics of this process under spatial confinement we used either PDMS pillars or micro-contact printing of vitronectin. OCT4, E-cadherin, and NANOG were progressively upregulated within about 70 µm from the outer rim of iPSC colonies. Single-cell RNA-sequencing demonstrated that OCT4high subsets have pronounced up-regulation of the TGF-β pathway, particularly of NODAL and its inhibitor LEFTY, at the rim of the colonies. Furthermore, calcium-dependent cell-cell interaction seemed to be relevant for the self-organization. After 5 to 7 days, the iPSC colonies detached spontaneously from micro-contact printed substrates to form 3D aggregates. This new method allowed generation of embryoid bodies (EBs) of controlled size, without any enzymatic or mechanical treatment. Within the early 3D aggregates, the radial organization and differential gene expression continued in analogy to the changes observed during self-organization of flat iPSC colonies. Our results provide further insight into the gradual self-organization within iPSC colonies and at their transition into EBs.
2022-08-26 | GSE184603 | GEO
Project description:Colonies of induced pluripotent stem cells (iPSCs) reveal aspects of self-organization even under culture conditions that maintain pluripotent state. To investigate the dynamics of this process under spatial confinement we used either PDMS pillars or micro-contact printing of vitronectin. OCT4, E-cadherin, and NANOG were progressively upregulated within about 70 µm from the outer rim of iPSC colonies. Single-cell RNA-sequencing demonstrated that OCT4high subsets have pronounced up-regulation of the TGF-β pathway, particularly of NODAL and its inhibitor LEFTY, at the rim of the colonies. Furthermore, calcium-dependent cell-cell interaction seemed to be relevant for the self-organization. After 5 to 7 days, the iPSC colonies detached spontaneously from micro-contact printed substrates to form 3D aggregates. This new method allowed generation of embryoid bodies (EBs) of controlled size, without any enzymatic or mechanical treatment. Within the early 3D aggregates, the radial organization and differential gene expression continued in analogy to the changes observed during self-organization of flat iPSC colonies. Our results provide further insight into the gradual self-organization within iPSC colonies and at their transition into EBs.
2022-08-26 | GSE160665 | GEO
Project description:Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13+ basal and Krt15+ club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
2024-01-19 | PXD039508 | Pride
Project description:Low grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial atypia) is one of the earliest morphologically recognizable neoplastic lesions of the breast. Frequently, it occurs in association with lobular intraepithelial neoplasia (LIN). The aim of this study was to elucidate chromosomal aberrations in these early neoplastic breast lesions using array comparative genomic hybridization (CGH) analysis. Laser capture microdissection of 12 archival formalin-fixed, paraffin-embedded specimens harbouring both foci of DIN1a as well as LIN was performed. All analyzed cases of DIN1a and LIN showed chromosomal gains and losses. The aberration encountered most often was loss on 16q in 7 DIN1a (70%) and 10 LIN (91%) cases. Regarding changes in chromosome 1, four DIN1a (40%) and 7 LIN (64%) cases showed a gain on 1q. The results of our study show concurrent chromosomal aberrations of 1q gains and 16q losses in several cases with coexisting LIN and low grade flat DIN. These aberrations are known to be common in low grade invasive ductal carcinomas as well as more advanced (conventional) types of low grade DIN (low grade ductal carcinoma in-situ). Our results raise the possibility of similar molecular-genetic pathways in most of the cases with coexisting LIN and low grade flat DIN.
2010-05-05 | GSE18187 | GEO