CROP-seq of hiPSC-derived astrocytes (bulk RNA-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA755724 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CROP-seq of hiPSC-derived astrocytes
| PRJNA755719 | ENA
Project description:CROP-seq of hiPSC-derived astrocytes (scRNA-Seq)
| PRJNA755725 | ENA
Project description:In response to central nervous system injury or disease, astrocytes become reactive, adopting context-dependent states with altered functions. Certain inflammatory insults induce reactive astrocyte states that lose homeostatic functions and gain neurotoxicity, and likely contribute to neuroinflammatory and neurodegenerative diseases. However, the cellular pathways controlling these states are not fully understood. Here, we combined single-cell transcriptomics with CRISPRi screening in human iPSC-derived astrocytes to systematically interrogate inflammatory reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-kB activation drove two distinct inflammatory reactive states dependent on STAT3 and IRF1, respectively. Furthermore, these states corresponded with those observed in other experimental contexts, including in vivo, and their markers were upregulated in the human brain in Alzheimer's disease and ischemic-hypoxic encephalopathy. These results and the platform we established have the potential to guide the development of therapeutics to selectively modulate different aspects of inflammatory astrocyte reactivity.
2021-08-24 | GSE182307 | GEO
Project description:In response to central nervous system injury or disease, astrocytes become reactive, adopting context-dependent states with altered functions. Certain inflammatory insults induce reactive astrocyte states that lose homeostatic functions and gain neurotoxicity, and likely contribute to neuroinflammatory and neurodegenerative diseases. However, the cellular pathways controlling these states are not fully understood. Here, we combined single-cell transcriptomics with CRISPRi screening in human iPSC-derived astrocytes to systematically interrogate inflammatory reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-kB activation drove two distinct inflammatory reactive states dependent on STAT3 and IRF1, respectively. Furthermore, these states corresponded with those observed in other experimental contexts, including in vivo, and their markers were upregulated in the human brain in Alzheimer's disease and ischemic-hypoxic encephalopathy. These results and the platform we established have the potential to guide the development of therapeutics to selectively modulate different aspects of inflammatory astrocyte reactivity.
2021-08-24 | GSE182308 | GEO
Project description:Five hiPSC lines from four individuals were differentiated to neural progenitor cells. The two cell types were compared in regards to marker gene expression of known cell type markers to show that the used bulk RNA-seq protocol, called prime-seq can capture known biological differences.
2021-08-01 | E-MTAB-10133 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-08-24 | GSE182309 | GEO
Project description:To investigate HCM mutation-associated molecular details at the early stage of disease development, we performed bulk RNA-seq analysis at Day 15 of differentiation using RNA isolated from the isogenic control and mutant hiPSC-CMs. We performed pair-end sequencing with >30 million reads per sample with clean read counts of more than 96% for each sample.
2022-07-06 | GSE198258 | GEO
Project description:Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. Using this method, we generated hiPSC-derived astrocyte populations (hiPSC-astrocytes) from 42 NPC lines (derived from 30 individuals) with an average of ~90% S100β-positive cells. Transcriptomic analysis demonstrated that the hiPSC-astrocytes are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our novel protocol is a reproducible, straightforward (single media) and rapid (<30 days) method to generate homogenous populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.
2017-08-18 | GSE97904 | GEO
Project description:Non-neuronal cells, including astrocytes, play a crucial role in the selective motor neuron pathology in amyotrophic lateral sclerosis (ALS). How astrocytes exactly contribute to the disease is not fully elucidated. Therefore, we characterised human induced pluripotent stem cell (hiPSC)-derived astrocytes from FUS-ALS patients, and incorporated these astrocytes into a human motor unit model to investigate the astrocytic effect on hiPSC-derived motor neuron network and neuromuscular junctions (NMJs). We observed a dysregulation of astrocyte homeostasis, which resulted in a FUS-ALS-mediated increase in reactivity and secretion of pro-inflammatory cytokines. Upon coculture with motor neurons and myotubes, we detected a cytotoxic effect on motor neuron-neurite morphology and outgrowth, as well as on NMJ formation and functionality, which was improved or fully rescued by isogenic control astrocytes. We conclude that mutant astrocytes have both a gain-of-toxicity and loss-of-support function in ALS, ultimately contributing to the disruption of motor neuron homeostasis, intercellular networks and NMJs.
2023-01-19 | GSE196219 | GEO
Project description:We used PIP-seq with a CROP-seq library to evaluate the feability of PIP-seq for large pooled CRISPR screens
2023-01-12 | GSE202915 | GEO