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Effect of DGCR8 heterozygosity on steady state RNA levels in embryonic teratocarcinoma PA-1 cells

ABSTRACT: In this dataset we use total RNA-seq to study the effect of DGCR8 heterozygosity on steady state RNA levels

ORGANISM(S): Homo sapiens

PROVIDER: GSE197472 | GEO | 2025/02/14

REPOSITORIES: GEO

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Effect of DGCR8 heterozygosity on steady state miRNA levels in embryonic teratocarcinoma PA-1 cells

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DGCR8 haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects

Project description:The 22q11.2 deletion syndrome (22qDS) is caused by a microdeletion in one of the chromosomes 22, comprising around 40 genes and including DGCR8, an essential gene for miRNA biogenesis and transposable elements control. Most of the clinical manifestations of 22qDS have their origin during embryonic development, but the contribution of human DGCR8 hemizygosity to the disease is unknown. To clarify the overall effect of DGCR8 in the context of 22qDS, we have generated two human embryonic models of DGCR8 +/-.In this dataset we use small RNA-seq to study the effect of DGCR8 heterozygosity on steady state miRNA levels in human embryonic stem cells.

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Project description:The 22q11.2 deletion syndrome (22qDS) is caused by a microdeletion in one of the chromosomes 22, comprising around 40 genes and including DGCR8, an essential gene for miRNA biogenesis and transposable elements control. Most of the clinical manifestations of 22qDS have their origin during embryonic development, but the contribution of human DGCR8 hemizygosity to the disease is unknown. To clarify the overall effect of DGCR8 in the context of 22qDS, we have generated two human embryonic models of DGCR8 +/-.In this dataset we use total RNA-seq to study the effect of DGCR8 heterozygosity on steady state RNA levels in human embryonic stem cells.

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The role of DGCR8 in RNA processing in human embryonic teratocarcinoma PA-1 cells.The role of DGCR8 in RNA processing in human embryonic teratocarcinoma PA-1 cells.

Project description:The role of DGCR8 in RNA processing in human embryonic teratocarcinoma PA-1 cells.The role of DGCR8 in RNA processing in human embryonic teratocarcinoma PA-1 cells.

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The role of DGCR8 in RNA processing in human embryonic teratocarcinoma PA-1 cells.The role of DGCR8 in RNA processing in human embryonic teratocarcinoma PA-1 cells.

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-02-14 | GSE197474 | GEO

Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis

Project description:DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domains. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1 Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA processing-independent role for DGCR8 in maintaining heterochromatin organization and attenuating senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.

2019-05-28 | PXD013856 | Pride

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