Regional gene expression profiling upon loss of NFIA in adult astrocytes
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ABSTRACT:
PROVIDER: PRJNA608957 | ENA |
REPOSITORIES: ENA
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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
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
Project description:Regional spinal cord gene expression profiling of adult astrocytes
| PRJNA773753 | ENA
Project description:Differentiation of astrocytes from human pluripotent stem cells (hPSCs) is a tedious and variable process. This hampers the study of hPSC-generated astrocytes in disease processes and drug development. By using CRISPR/Cas9-mediated inducible expression of NFIA or NFIA plus SOX9 in hPSCs, we developed a method to efficiently generate astrocytes in 4-7 weeks. The astrocytic identity of the induced cells was verified by their characteristic molecular and functional properties as well as after transplantation. Furthermore, we developed a strategy to generate region-specific astrocyte subtypes by combining differentiation of regional progenitors and transgenic induction of astrocytes. This simple and efficient method offers a new opportunity to study the fundamental biology of human astrocytes and their roles in disease processes.
2018-08-11 | GSE118384 | GEO
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
Project description:The goal of this study is to determine how the loss of the transcription factor Sox9 affects the molecular profiles of adult astrocytes from the olfactory. We performed RNA-sequencing on wildtype and Sox9 knockout (KO) astrocytes from the olfactory bulb and analyzed the molecular signatures of Sox9 KO astrocytes compared to the wildtype control.
2021-07-28 | GSE180841 | GEO
Project description:Olfactory bulb gene expression profiling upon loss of Sox9 in adult astrocytes
| PRJNA749762 | ENA
Project description:There is emerging evidence that astrocytes exhibit molecular and cellular heterogeneity; however, whether distinct subpopulations perform these diverse roles remains poorly defined. Previous studies used Aldhl1l1 as a bulk astrocyte marker. Here we show that the Lunatic Fringe-GFP (Lfng-GFP) bacteria artificial chromosome mouse line specifically labels astrocyte populations within lamina III and IV of the dorsal spinal cord. We compared the transcriptional profile of Lfng-GFP+ astrocytes with Aldh1l1-GFP astrocytes to identify what is unique about the astrocyte population.
2021-10-25 | GSE186410 | GEO
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
Project description:Intracellular trafficking is essential for proper cell signaling. In the pancreas, secretory cells rely on trafficking to regulate blood glucose and digestion. Pancreatic disorders reflect defects in function or development, evoking considerable interest in understanding the molecular genetics governing pancreatic organogenesis. Here, we show the transcription factor NFIA regulates trafficking in both the embryonic and adult pancreas, affecting both developmental cell fate decisions and adult physiology. NFIA deletion from pancreatic progenitors led to the development of more acinar cells and ducts and fewer endocrine cells, whereas ectopic NFIA promoted endocrine formation. We found that NFIA’s effects on trafficking influence endocrine/exocrine cell fate decisions through regulation of Notch. Adult NFIA-deficient mice develop diabetic phenotypes due to impaired insulin granule trafficking and defects in acinar zymogen secretion. This study shows how a single transcription factor, NFIA, thus exerts profound effects on both embryonic cell fate and adult physiology by regulating vesicle trafficking.
2017-09-14 | GSE86909 | GEO