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Human iPSC derived posterior gut progenitors are expandable and capable of forming gut and liver organoids

ABSTRACT: Human iPSC derived posterior gut progenitors are expandable and capable of forming gut and liver organoids

PROVIDER: PRJNA429203 | ENA |

REPOSITORIES: ENA

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Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids.

Project description:Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm. We found that combinatorial EGF, VEGF, FGF2, Chir99021, and A83-01 treatments selectively amplify storable PGECs up to 1021 cell scale without any gene transduction or feeder use. PGECs, compared with induced pluripotent stem cells, showed stable differentiation propensity into multiple endodermal lineages without teratoma formation. Furthermore, transplantation of PGEC-derived liver bud organoids showed therapeutic potential against fulminant liver failure. Together, the robustly amplified PGECs may be a promising cellular source for endoderm-derived organoids in studying human development, modeling disease, and, ultimately, therapy.

| S-EPMC5919071 | biostudies-literature

Human iPSC derived posterior gut progenitors are expandable and capable of forming gut and liver organoids

Project description:Organoid technology provides a revolutionary paradigm towards therapy, yet to be applied in humans mainly because of the reproducibility and scalability challenges. Here, we overcome these limitations by evolving scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive ‘reverse’ screen experiments, we identified effective triple progenitor populations for generating liver buds in a highly reproducible manner: hepatic endoderm, endothelial and septum mesenchyme progenitors. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass-producing homogenous and miniaturized liver buds on a clinically relevant large scale (>108-cell scale). Vascularized and functional liver tissues generated entirely from iPSC significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacture platform for multi-cellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.

2018-01-10 | GSE108937 | GEO

Kidney organoids are capable of forming Wilms-like tumors, but not teratomas

Project description:Kidney organoids are capable of forming Wilms-like tumors, but not teratomas

| PRJNA693847 | ENA

Generation of human iPS cell-derived mesenchymal cells capable of forming alveolar organoids

Project description:Generation of human iPS cell-derived mesenchymal cells capable of forming alveolar organoids

| PRJNA780470 | ENA

Integrative multi-omics increase resolution of the sea urchin posterior gut gene regulatory network at the single-cell level

Project description:We use multi-omics (ATAC-seq, single cell RNA-seq and differential bulk RNA-seq) to increase resolution of the sea urchin posterior gut GRN for the cells expressing the ParaHox gene Sp-Pdx1.

2024-08-06 | GSE262916 | GEO

Generation of human iPS cell-derived mesenchymal cells capable of forming alveolar organoids [scRNA-Seq]

Project description:Generation of human iPS cell-derived mesenchymal cells capable of forming alveolar organoids [scRNA-Seq]

| PRJNA780480 | ENA

Generation of human iPS cell-derived mesenchymal cells capable of forming alveolar organoids [bulkRNA-Seq]

Project description:Generation of human iPS cell-derived mesenchymal cells capable of forming alveolar organoids [bulkRNA-Seq]

| PRJNA780481 | ENA

Gene expression analyses of expandable hepatocytes in culture

Project description:To compare the global expression profiles among primary hepatocytes and expandable hepatocytes with or without in vitro differentiation.

2015-11-18 | GSE75141 | GEO

Transcription factor–mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells

Project description:Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to ‘induced’ oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphologyical and global gene expression profile molecular features consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into induced multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelinmyelinating axons both in vitro and in vivo. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies. 6 total samples were analyzed. MEFs were either untreated or infected with inducible lentiviral vectors containing the open reading frames of transcription factors. Samples were compared to bona fide OPCs.

2013-04-14 | E-GEOD-45440 | biostudies-arrayexpress

Flare Type Self-expandable Metal Stent for Malignant Colorectal Obstruction

Project description:This study compares flare type self-expandable metal stent with conventional D-type self-expandable metal stent for malignant colorectal obstruction.

| 2278863 | ecrin-mdr-crc

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