Dataset Information

Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain.

ABSTRACT: Astrocytes are the most abundant type of glial cell in the central nervous system and perform a myriad of vital functions, however, the nature of their diversity remains a longstanding question in neuroscience. Using transcription factor motif discovery analysis on region-specific gene signatures from astrocytes we uncovered universal and region-specific transcription factor expression profiles. This analysis revealed that motifs for Nuclear Factor-I (NFI) are present in genes enriched in astrocytes from all regions, with NFIB and NFIX exhibiting pan-astrocyte expression in the olfactory bulb, hippocampus, cortex, and brainstem. Further analysis into region-specific motif patterns, identified Nkx3-1, Stat4, Pgr, and Nkx6-1 as prospective region-specific transcription factors. Validation studies revealed that Nkx6-1 is exclusively expressed in astrocytes in the brainstem and associates with the promoters of several brainstem specific target genes. These studies illustrate the presence of multiple transcriptional layers in astrocytes across diverse brain regions and provide a new entry point for examining how astrocyte diversity is specified and maintained.

SUBMITTER: Lozzi B

PROVIDER: S-EPMC7046629 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain.

Lozzi Brittney B Huang Teng-Wei TW Sardar Debosmita D Huang Anna Yu-Szu AY Deneen Benjamin B

Frontiers in neuroscience 20200221

Astrocytes are the most abundant type of glial cell in the central nervous system and perform a myriad of vital functions, however, the nature of their diversity remains a longstanding question in neuroscience. Using transcription factor motif discovery analysis on region-specific gene signatures from astrocytes we uncovered universal and region-specific transcription factor expression profiles. This analysis revealed that motifs for Nuclear Factor-I (NFI) are present in genes enriched in astroc ...[more]

PMID: 32153350

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Project description:INTRODUCTION:Recently, multicellular spheroids were isolated from a well-established epithelial ovarian cancer cell line, OVCAR-3, and were propagated in vitro. These spheroid-derived cells displayed numerous hallmarks of cancer stem cells, which are chemo- and radioresistant cells thought to be a significant cause of cancer recurrence and resultant mortality. Gene set enrichment analysis of expression data from the OVCAR-3 cells and the spheroid-derived putative cancer stem cells identified several metabolic pathways enriched in differentially expressed genes. Before this, there had been little previous knowledge or investigation of systems-scale metabolic differences between cancer cells and cancer stem cells, and no knowledge of such differences in ovarian cancer stem cells. METHODS:To determine if there were substantial metabolic changes corresponding with these transcriptional differences, we used two-dimensional gas chromatography coupled to mass spectrometry to measure the metabolite profiles of the two cell lines. RESULTS:These two cell lines exhibited significant metabolic differences in both intracellular and extracellular metabolite measurements. Principal components analysis, an unsupervised dimensional reduction technique, showed complete separation between the two cell types based on their metabolite profiles. Pathway analysis of intracellular metabolomics data revealed close overlap with metabolic pathways identified from gene expression data, with four out of six pathways found enriched in gene-level analysis also enriched in metabolite-level analysis. Some of those pathways contained multiple metabolites that were individually statistically significantly different between the two cell lines, with one of the most broadly and consistently different pathways, arginine and proline metabolism, suggesting an interesting hypothesis about cancerous and stem-like metabolic phenotypes in this pair of cell lines. CONCLUSIONS:Overall, we demonstrate for the first time that metabolism in an ovarian cancer stem cell line is distinct from that of more differentiated isogenic cancer cells, supporting the potential importance of metabolism in the differences between cancer cells and cancer stem cells.

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Dataset Information

Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain.

Publications

Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain.

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