Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells

ABSTRACT: NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells

PROVIDER: PRJNA412090 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6074300_1.fastq.gz	Fastqsanger.gz
	SRR6074300_2.fastq.gz	Fastqsanger.gz
	SRR6074310_1.fastq.gz	Fastqsanger.gz
	SRR6074310_2.fastq.gz	Fastqsanger.gz
	SRR6074320_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 120

Similar Datasets

NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells

Project description:The development of the central nervous system (CNS) depends on the orchestrated generation of neurons and glia from neural stem cells (NSCs). Although NSCs generate both cell types, they are produced sequentially as neurons are born first and glia later. In humans, this timing is extremely protracted and the underlying mechanisms remain unknown. Deriving glial cells such as astrocytes from human pluripotent stem cells requires 3-6 months of differentiation, greatly impeding their use in human disease modeling and regenerative medicine. Here, we report that expression of the transcription factor nuclear factor IA (NFIA) is sufficient to trigger glial competency in highly neurogenic NSCs and enables the derivation of human astrocytes within 10-12 days. NFIA-induced astrocytes are functional and shown to promote synaptogenesis, protect neurons and generate calcium transients. The mechanism of NFIA-induced glial competency involves rapid but reversible chromatin remodeling, demethylation of the GFAP promoter and a striking effect on the cell cycle. NFIA titration and pharmacological studies indicate that acquisition of a glial-compatible G1 length is critical for achieving glial competency. Our results offer mechanistic insights into human glial competency and enable the routine use of astrocytes for studying human development and disease.

2019-02-25 | GSE104232 | GEO

NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells.

Project description:The mechanistic basis of gliogenesis, which occurs late in human development, is poorly understood. Here we identify nuclear factor IA (NFIA) as a molecular switch inducing human glial competency. Transient expression of NFIA is sufficient to trigger glial competency of human pluripotent stem cell-derived neural stem cells within 5 days and to convert these cells into astrocytes in the presence of glial-promoting factors, as compared to 3-6 months using current protocols. NFIA-induced astrocytes promote synaptogenesis, exhibit neuroprotective properties, display calcium transients in response to appropriate stimuli and engraft in the adult mouse brain. Differentiation involves rapid but reversible chromatin remodeling, glial fibrillary acidic protein (GFAP) promoter demethylation and a striking lengthening of the G1 cell cycle phase. Genetic or pharmacological manipulation of G1 length partially mimics NFIA function. We used the approach to generate astrocytes with region-specific or reactive features. Our study defines key mechanisms of the gliogenic switch and enables the rapid production of human astrocytes for disease modeling and regenerative medicine.

| S-EPMC6591152 | biostudies-literature

Identification of Nfia-target genes in mid-gestational NS/PCs

Project description:The purpose of this study is to identify Nfia-target genes, and then clarify how Nifa induces gliogenic potential during brain development.

2021-04-15 | GSE164503 | GEO

Regional gene expression profiling upon loss of NFIA in adult astrocytes

Project description:The goal of this study is to determine how the loss of the transcription factor NFIA affects the molecular profiles of adult astrocytes from four brain regions. We performed RNA-sequencing on control and NFIA knockout (KO) astrocytes from the olfactory bulb, hippocampus, cortex, and brainstem, and analyzed the molecular signatures of NFIA KO astrocytes compared to control in each brain region.

2020-02-27 | GSE146000 | GEO

Mouse ESC-derived NSPCs NFIA OE (miRNA)

Project description:Since the NFI transcription factors have been shown to be key regulators of gliogenesis, we utilized this pathway to identify miRNAs involved in the regulation of the neurogenesis-to-gliogenesis switch by neural stem/progenitor cells (NSPCs). We focused on miRNAs with expression levels that were differentially regulated downstream of NFIA, and established a mouse embryonic stem cell (ESC) line that expresses NFIA in a doxycycline (Dox)-dependent manner. NFIA-overexpressing (OE) and control NSPCs (neurospheres) derived from ESCs were purified from their mixed cultures (primary neursphsres (PNs) or secondary neurospheres (SNs) ) by fluorescence activated cell sorting and subjected to miRNAarray analysis.

2015-08-01 | E-GEOD-70128 | biostudies-arrayexpress

Mouse ESC-derived NSPCs NFIA OE (GE)

2015-08-01 | E-GEOD-70130 | biostudies-arrayexpress

Region-specific DNA-binding properties of NFIA in the adult mouse brain

Project description:The goal of this study is to profile NFIA DNA-binding properties in the adult mouse brain. We performed chromatin immunoprecipitation of NFIA in the hippocampus and olfactory bulb of wildtype mice, and samples were subjected to sequencing. We find that NFIA preferentially binds DNA in the hippocampus but not in the olfactory bulb as evidenced by the distinct lack of NFIA binding peaks in the olfactory bulb. Mass spectrometry results suggested that NFIA has a significantly higher binding affinity for NFIB in the olfactory bulb, potentially blocking NFIA’s ability to bind DNA. Virally induced siRNAs against NFIB or scramble were injected into the olfactory bulb of adult wildtype mice to knock down NFIB. We performed chromatin immunoprecipitation of NFIA in the olfactory bulb injected with siRNA-NFIB or siRNA-scramble. Subsequent sequencing revealed an increase of NFIA binding in the olfactory bulb upon the depletion of NFIB as compared to the siRNA-scramble and wildtype controls.

2020-02-28 | GSE146064 | GEO

Sequential expression profile of feeder-free iPSC-derived gliogenic NS/PCs by RNA-seq

Project description:We performed RNA sequencing to profile the temporal dynamics of gene expression during gliogenic NS/PC differentiation from human iPSCs.

2020-12-09 | GSE138301 | GEO

Mouse ESC-derived NSPCs NFIA OE (GE)

2015-08-01 | GSE70130 | GEO

Mouse ESC-derived NSPCs NFIA OE (miRNA)

2015-08-01 | GSE70128 | GEO