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Reliability of human retinal organoid generation from hiPSC-derived neuroepithelial cysts

ABSTRACT: Reliability of human retinal organoid generation from hiPSC-derived neuroepithelial cysts

PROVIDER: PRJNA993408 | ENA |

REPOSITORIES: ENA

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Reliability of human retinal organoid generation from hiPSC-derived neuroepithelial cysts

Project description:The application potential of human induced pluripotent stem cells (hiPSC) derived human retinal organoids (HRO) relies on the robustness and transferability of the methodology for their generation. Standardized strategies and parameters to effectively assess, compare and optimize organoid protocols have been started to be established, but are not completed yet. To advance this, we explored the efficiency and reliability of a differentiation protocol that facilitates retina generation by formation of neuroepithelial cysts from hiPSC clusters. Here, we tested seven different hiPSC lines, which reproducibly generated HROs. Histologic and ultrastructural analyses support regulated HRO differentiation and maturation. The different hiPSC lines appeared to be a larger source of variance than experimental rounds. Whereas previous reports showed that HRO in several other protocols contain a rather low numbers of cones compared to rods, HROs derived by the cyst protocol consistently are cone-richer and with an comparable ratio of cones, rods, and Müller glia. Additionally, we devised a potential strategy to systematically evaluate different protocols side-by-side through parallel differentiation from the same hiPSC batches: The cyst-protocol was compared to a conceptually different protocol based on cell aggregate formation from single hiPSCs. Comparison of four hIPSC lines showed that both protocols reproduced key characteristics of retinal epithelial structure and cell composition, but the cyst-protocol provided a higher HRO yield. Further, while cyst-derived HROs maintained stable at least up to date 250, whereas single hiPSC-derived HROs showed spontaneous pathologic changes already by day 200. Overall, our data provide insight into the efficiency, reproducibility, and stability of the cyst-protocol for HRO generation, which will be useful for further organoid system optimization, as well as basic and translational research applications.

2023-09-26 | GSE237007 | GEO

Multiome experiment of the neuroepithelial stage of brain organoid developement

Project description:To investigate the heterogeneity during the neuroepithelial stage of organoid development, we performed a multiome experiment on day 15-18 old brain organoids

2022-10-03 | E-MTAB-12004 | biostudies-arrayexpress

Multiome experiment of the neuroepithelial stage of brain organoid developement

Project description:Multiome experiment of the neuroepithelial stage of brain organoid developement

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Gene expression profiles of hiPSCs, hiPSC-drived neuroepithelial cells (NECs), and hiPSC-derived neural crest cells (NCCs).

Project description:Gene expression profiles of hiPSCs, hiPSC-drived neuroepithelial cells (NECs), and hiPSC-derived neural crest cells (NCCs).

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Reliability of 3D Cortical Spheroids Generation from Human Pluripotent Stem Cells

Project description:Here we assess the reliability of human cortical spheroid differentiation cultured in xeno-free, feeder-free conditions. We find high reliability in differentiation across multiple hiPSC lines as well as across experiments, and we anticipate that this directed differentiation approach will be useful for large scale generation of brain-region specific spheroids and disease modeling.

2018-11-06 | GSE120700 | GEO

Apically localized PANX1 impacts neuroepithelial expansion in human cerebral organoids

Project description:Dysfunctional paracrine signaling through Pannexin 1 (PANX1) channels is linked to several adult neurological pathologies and emerging evidence suggests that PANX1 plays an important role in human brain development. It remains unclear how early PANX1 influences brain development, or how loss of PANX1 alters the developing human brain. Using a cerebral organoid model of early human brain development, we find that PANX1 is expressed at all stages of organoid development from neural induction through to neuroepithelial expansion and maturation. Interestingly, PANX1 cellular distribution and subcellular localization changes dramatically throughout cerebral organoid development. During neural induction, PANX1 becomes concentrated at the apical membrane domain of neural rosettes where it co-localizes with several apical membrane adhesion molecules. During neuroepithelial expansion, PANX1-/- organoids are significantly smaller than control and exhibit significant gene expression changes related to cell adhesion, WNT signaling and non-coding RNAs. As cerebral organoids mature, PANX1 expression is significantly upregulated and is primarily localized to neuronal populations outside of the ventricular-like zones. Ultimately, PANX1 protein can be detected in all layers of a 21-22 post conception week human fetal cerebral cortex. Together, these results show that PANX1 is dynamically expressed by numerous cell types throughout embryonic and early fetal stages of human corticogenesis and loss of PANX1 compromises neuroepithelial expansion due to dysregulation of cell-cell and cell-matrix adhesion, perturbed intracellular signaling, and changes to gene regulation.

2023-12-12 | GSE249624 | GEO

SB431452 affects extracellular matrix during induction of hiPSC-derived gastric organoid with muscularis mucosa

Project description:SB431452 affects extracellular matrix during induction of hiPSC-derived gastric organoid with muscularis mucosa

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SB431452 affects extracellular matrix during induction of hiPSC-derived gastric organoid with muscularis mucosa

Project description:We report TGFβ signaling is involved in muscularis mucosa differentiation of hiPSC-derived gastric organoids.

2022-03-22 | GSE178441 | GEO

Expression data from renal cysts of autosomal dominant polycystic kidney disease (ADPKD) patients

Project description:To elucidate the molecular pathways that modulate renal cyst growth in autosomal dominant polycystic kidney disease (ADPKD) Keywords: Disease state analysis We performed global gene profiling on renal cysts of different size (small cysts: less than 1 ml, n=5; medium cysts: between 10-25 ml, n=5; large cysts: greater than 50 ml, n=3) and minimally cystic tissue (MCT, n=5) from five PKD1 polycystic kidneys. Additionally, non-cancerous renal cortical tissue from three nephrectomized kidneys with isolated renal cell carcinoma was used as normal control tissue (n=3). This dataset is part of the TransQST collection.

2009-08-14 | E-GEOD-7869 | biostudies-arrayexpress

Epigenome analysis of low-grade neuroepithelial tumors with FGFR2 fusions

Project description:Genome-wide DNA methylation profiling of 8 low-grade neuroepithelial tumors (LGNET) with FGFR2 fusions with various histologic diagnoses including ganglioglioma, multinodular and vacuolating neuronal tumor (MVNT), low-grade glioneuronal tumor NOS, and polymorphous low-grade neuroepithelial tumor of the young (PLNTY). The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 8 low-grade neuroepithelial tumors with FGFR2 fusions.

2021-07-27 | GSE172081 | GEO

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