Project description:Single cell RNA-seq characterization of human induced pluripotent stem cells-derived human cortical organoids (hCO) cultured in control and XG-supplemented conditions Reference: Narazaki, Genta; Miura, Yuki; Pavlov, Sergey D.; Thete, Mayuri Vijay; Roth, Julien G.; Avar, Merve; Kim, Ji-il; Hudacova, Zuzana; Heilshorn, Sarah C.; Pașca, Sergiu P. Scalable production of human cortical organoids using a biocompatible polymer. GSE232581. DOI: (2025).
Project description:We generated cortical organoids from four FCD patients. To generate cortical organoids, we used induced pluriplotent stem cells (iPSCs) obtained from skin biopsy from these FCD selected patients and healthy controls. We extrated RNA samples from the cortical organoids to do customized panel of gene expression. Gene expression using NanoString Human Neuropathology Panel from four FCD patients and four controls
Project description:The application of organoids has been limited by the lack of methods for producing uniformly mature organoids at scale. This study introduces an organoid culture platform, called UniMat, which addresses the challenges of uniformity and maturity simultaneously. UniMat is designed to not only ensure consistent organoid growth but also facilitate an unrestricted supply of soluble factors by a 3D geometrically-engineered, permeable membrane-based platform. Using UniMat, we demonstrate the scalable generation of kidney organoids with enhanced uniformity in both structure and function compared to conventional methods. Notably, kidney organoids within UniMat matured significantly better, showing increased expression of nephron transcripts, more in vivo-like cell-type balance, and better vascularization. Moreover, UniMat's design offers a more standardized organoid model for drug testing, as demonstrated by its consistent response to a polycystic-kidney-disease drug. In essence, UniMat presents a transformative platform for organoid technology, promising applications in organ development, disease modeling, and drug screening.
Project description:Here we used human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Cortical organoids were differentiated as previously described (Paşca et al., 2015, doi: 10.1038/nmeth.3415.).Chronic GSK3 inhibition was performed by adding CHIR99021 (Merck SML1046) to the medium at day 0 (1 microM) and kept throughout the differentiation process until reaching the respective collection timepoints (day 18, day 50, day 100).
Project description:A method was developed to reproducibly produce neural retina and cortical brain regions from confluent cultures of stem cells. The spontaneously generated cortical organoids were isolated and cultured in suspension conditions for maturation. Proteomic analysis of both the original induced pluripotent stem cells and the cortical organoids demonstrated the increased presence of synaptic components, indicating maturity.
Project description:Organoid models have been developed for a number of tissues including the liver. Currenthepatic organoid models are generally simplistic, composed of hepatocytes orcholangiocytes, rendering them less physiologically relevant when compared to nativetissue. To address this we have developed an approach that does not require 2Dpatterning, which is ECM independent and growth factor free, to mimic embryonic liverdevelopment that produces massive quantities of liver like organoids. Using single-cell RNAsequencing and immunofluorescence we demonstrate a liver-like cellular repertoire,presenting with vascular luminal structures,and a population of resident macrophage – theKupffer cells. The organoids exhibit key liver functions including drug metabolism, serumprotein production, urea synthesis and coagulation factor production, which preservedpost-translational modifications such as N-glycosylation and functionality. The organoidscan be transplanted and maintained inmice producing human albumin long term.Theorganoids exhibit a complex cellular repertoire reflective of the organ, havede novovascularization, and liver like function. This isa pre-requisite for a myriad of applicationsfrom cellular therapy, tissue engineering, drug toxicity assessment, disease modeling, tobasic developmental biology.