Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human fetal brain self-organizes into long-term expanding organoids (bulk RNA-Seq)

ABSTRACT: Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

ORGANISM(S): Homo sapiens

PROVIDER: GSE248479 | GEO | 2024/01/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Human fetal brain self-organizes into long-term expanding organoids (scRNA-Seq)

Project description:Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

2024-01-08 | GSE248480 | GEO

Human fetal brain self-organizes into long-term expanding organoids

Project description:Human fetal brain self-organizes into long-term expanding organoids

| PRJNA1044104 | ENA

Human fetal brain self-organizes into long-term expanding organoids (scRNA-Seq)

Project description:Human fetal brain self-organizes into long-term expanding organoids (scRNA-Seq)

| PRJNA1044106 | ENA

Human fetal brain self-organizes into long-term expanding organoids (bulk RNA-Seq)

Project description:Human fetal brain self-organizes into long-term expanding organoids (bulk RNA-Seq)

| PRJNA1044107 | ENA

A brain organoid/ALL co-culture model reveals the AP-1 pathway as critically associated with CNS-involvement of BCP-ALL

Project description:Central nervous system (CNS) involvement remains a clinical hurdle in treating childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The disease mechanisms of CNS leukemia are primarily investigated using 2D cell culture and mouse models. Given the variations in cellular identity and architecture between the human and murine CNS, it becomes imperative to seek complementary models to study CNS leukemia. Here, we present a first-of-its-kind 3D co-culture model combining human brain organoids and BCP-ALL cells. We noticed signicantly higher engraftment of TCF3::PBX1+ leukemia cell lines and patient-derived xenograft (PDX) cells in human induced pluripotent stem cell (iPSC)-derived cerebral organoids when compared to cell lines derived from chronic myeloid leukemia (CML), a subtype typically not associated with CNS involvement. Next, to validate translatability between organoid co-culture model and in vivo murine models, we confirmed that targeting CNS leukemia relevant pathways like CD79a/Igα or CXCR4-SDF1 reduced the invasion of BCP-ALL cells into organoids. RNA sequencing and further validations of organoid-invading leukemia cells compared to the non-invaded fraction revealed significant upregulation of the AP-1 transcription factor-complex members in organoid-invading cells. Moreover, we detected a significant enrichment of AP-1 pathway genes in ALL-PDX cells recovered from the CNS compared to spleen blasts of mice transplanted with TCF3::PBX1+ PDX cells, substantiating the role of AP-1 signaling in CNS disease. Accordingly, we found significantly higher levels of the AP-1-gene JUN in patients initially diagnosed as CNS-positive compared to CNS-negative cases as well as CNS-relapse cases in a cohort of 100 BCP-ALL patients. Our results suggest iPSC-derived brain organoids as a novel model to investigate CNS-involvement and identify the AP-1 pathway as a critical driver of CNS-disease in BCP-ALL.

2024-07-16 | GSE271998 | GEO

Transcriptome profiling of organoids from the human and murine gastrointestinal tract

Project description:The epithelial layer of the gastrointestinal tract is the body’s first line of defense against gut pathogens. However, our current understanding of the innate immune response of the epithelial layer is limited. For this study, we used gastrointestinal organoids which have the advantage of being primary, non-transformed epithelium that retains organ-specific characteristics in culture, and also that they lack any confounding immune cells. We systematically profiled the transcriptomes of gastrointestinal epithelial cells using a newly generated biobank of human and murine GI organoids grown from tissue-resident stem cells, providing an atlas of gene expression along the GI tract of both species. RNA sequencing of all lines confirmed the preservation of tissue identity, and in addition revealed extensive organization of innate immune signaling components along the cephalocaudal axis, endowing a specific innate immune profile to each segment.

2020-05-23 | GSE127938 | GEO

Tissue architecture influences brain organoid identity and developmental trajectory

Project description:This project used snRNA-seq and Molecular Cartography (single cell spatial transcriptomics) to investigate the relation between morphology and molecular identity in human brain organoids.

2022-09-16 | E-MTAB-11564 | biostudies-arrayexpress

Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease

Project description:Picornaviruses are a leading cause of central nervous system (CNS) infections. While genotypes such as Parechovirus A3 (PeV-A3) and echovirus 11 (E11) can elicit severe neurological disease, the highly prevalent PeV-A1 is not associated with CNS disease. Here, we expand our current understanding of these differences in PeV-A CNS disease using human brain organoids and clinical isolates of PeV-A genotypes. Our data indicates that PeV-A1 and A3 specific differences in neurological disease are not due to infectivity of CNS cells as both viruses productively infect brain organoids with a similar cell tropism. Proteomic analysis showed that PeV-A infection significantly alters the host cell metabolism. The inflammatory response following PeV-A3 (and E11 infection) was significantly more potent than that upon PeV-A1 infection. Collectively, our findings align with clinical observations and suggest a role for inflammatory-mediated neurology, rather than viral replication, in PeV-A3 (and E11) infection.

2024-02-14 | PXD047238 | Pride

Molecular features of the measles virus viral fusion complex that favor infection and spread in the brain [mouse]

Project description:A measles virus (MeV) isolate bearing a single amino acid change in the fusion protein (F) -- L454W -- was identified in two patients who died of MeV central nervous system (CNS) infection. We analyzed whether this mutation confers an advantage over wild type virus in the CNS, thereby contributing to disease in these patients. Using murine ex vivo organotypic brain cultures and human induced pluripotent stem cell-derived brain organoids, we show that specific CNS adaptive mutations in F result in augmented spread of virus ex vivo and that this is associated with an enhanced innate immune response. The spread of virus in brain organoids is blocked by an inhibitory peptide that targets F, confirming that dissemination in the brain tissue is attributable to F. A single mutation in MeV F thus alters the fusion complex to render the virus more neuropathogenic, allowing it to propagate in the face of the innate immune response.

2020-08-08 | GSE155885 | GEO

Molecular features of the measles virus viral fusion complex that favor infection and spread in the brain [human]

2020-08-08 | GSE155884 | GEO