Subsets of GSE239662 - Novel method of isolating nuclei of human oligodendrocyte precursor cells reveals substantial developmental changes in gene expression and H3K27ac histone modification. [RNA-Seq]
Description: |
Oligodendrocyte precursor cells (OPCs) generate differentiated mature oligodendrocytes (MOs) during development. In adult brain, OPCs replenish MOs in adaptive plasticity, neurodegenerative disorders, and after trauma. The ability of OPCs to differentiate to MOs decreases with age and is compromised in disease. Here we explored the cell specific and age-dependent differences in gene expression and H3K27ac histone mark in these two cell types. H3K27ac is indicative of active promoters and enhancers. We developed a novel flow-cytometry-based approach to isolate OPC and MO nuclei from human postmortem brain and profiled gene expression and H3K27ac in adult and infant OPCs and MOs genome-wide.In adult brain, we detected extensive H3K27ac differences between the two cell types with high concordance between gene expression and epigenetic changes. Notably, the expression of genes that distinguish MOs from OPCs appears to be under a strong regulatory control by the H3K27ac modification in MOs but not in OPCs. Comparison of gene expression and H3K27ac between infants and adults uncovered numerous developmental changes in each cell type, which were linked to several biological processes, including cell proliferation and glutamate signaling. A striking example was a subset of histone genes that were highly active in infant samples but fully lost activity in adult brain. Our findings demonstrate a considerable rearrangement of the H3K27ac landscape that occurs during the differentiation of OPCs to MOs and during postnatal development of these cell types, which aligned with changes in gene expression. The uncovered regulatory changes justify further in-depth epigenetic studies of OPCs and MOs in development and disease.
At time of import, last updated (by provider) on: Nov 01 2023
Contributors: ; [Alexey Kozlenkov, Stella Dracheva]
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Accession: | GSE239662 ![]() |
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Publication: | Kozlenkov, Alexey et al. (2024) ![]() ![]() |
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Dimension: | 40362 (39 samples) | |||||
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Assays: | Subject_2 Mature Oligodendrocytes RNA-seq Subject_17 Mature Oligodendrocytes RNA-seq Subject_12 Mature Oligodendrocytes RNA-seq Subject_6 Oligodendrocyte Precursor Cells RNA-seq Subject_1 Mature Oligodendrocytes RNA-seq Subject_20 Mature Oligodendrocytes RNA-seq Subject_17 Oligodendrocyte Precursor Cells RNA-seq Subject_21 Mature Oligodendrocytes RNA-seq Subject_21 Oligodendrocyte Precursor Cells RNA-seq Subject_20 Oligodendrocyte Precursor Cells RNA-seq Subject_19 Oligodendrocyte Precursor Cells RNA-seq Subject_25 Oligodendrocyte Precursor Cells RNA-seq Subject_11 Mature Oligodendrocytes RNA-seq Subject_6 Mature Oligodendrocytes RNA-seq Subject_18 Oligodendrocyte Precursor Cells RNA-seq Subject_23 Oligodendrocyte Precursor Cells RNA-seq Subject_25 Mature Oligodendrocytes RNA-seq Subject_1 Oligodendrocyte Precursor Cells RNA-seq Subject_12 Oligodendrocyte Precursor Cells RNA-seq Subject_14 Oligodendrocyte Precursor Cells RNA-seq Subject_22 Oligodendrocyte Precursor Cells RNA-seq Subject_3 Oligodendrocyte Precursor Cells RNA-seq Subject_10 Oligodendrocyte Precursor Cells RNA-seq Subject_11 Oligodendrocyte Precursor Cells RNA-seq Subject_23 Mature Oligodendrocytes RNA-seq Subject_3 Mature Oligodendrocytes RNA-seq Subject_13 Mature Oligodendrocytes RNA-seq Subject_22 Mature Oligodendrocytes RNA-seq Subject_19 Mature Oligodendrocytes RNA-seq Subject_7 Mature Oligodendrocytes RNA-seq Subject_24 Oligodendrocyte Precursor Cells RNA-seq Subject_13 Oligodendrocyte Precursor Cells RNA-seq Subject_7 Oligodendrocyte Precursor Cells RNA-seq Subject_15 Oligodendrocyte Precursor Cells RNA-seq Subject_16 Oligodendrocyte Precursor Cells RNA-seq Subject_10 Mature Oligodendrocytes RNA-seq Subject_24 Mature Oligodendrocytes RNA-seq Subject_2 Oligodendrocyte Precursor Cells RNA-seq Subject_18 Mature Oligodendrocytes RNA-seq |