The mediator subunit Med23 serves as a gatekeeper of the myeloid-primed state of hematopoietic stem cells (RNA-Seq)
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ABSTRACT:
PROVIDER: PRJNA445740 | ENA |
REPOSITORIES: ENA
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Project description:To ensure the rapid response to stimuli, some HSCs are specifically prepared (primed) for tasks involving activation and reconstitution. However, the key factors that regulate the primed state of HSCs are largely unknown. Here we report that Med23 controls the formation of myeloid-primed HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Moreover, Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are in myeloid-primed state and are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is down-regulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identified Med23 as a gatekeeper of the myeloid-primed state of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid-primed state of HSCs and HSC activation upon stresses.
2018-07-15 | GSE112358 | GEO
Project description:To ensure the rapid response to stimuli, some HSCs are specifically prepared (primed) for tasks involving activation and reconstitution. However, the key factors that regulate the primed state of HSCs are largely unknown. Here we report that Med23 controls the formation of myeloid-primed HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Moreover, Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are in myeloid-primed state and are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is down-regulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identified Med23 as a gatekeeper of the myeloid-primed state of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid-primed state of HSCs and HSC activation upon stresses.
2018-07-15 | GSE112357 | GEO
Project description:The mediator subunit Med23 serves as a gatekeeper of the myeloid-primed state of hematopoietic stem cells
| PRJNA445738 | ENA
Project description:The mediator subunit Med23 serves as a gatekeeper of the myeloid-primed state of hematopoietic stem cells (ATAC-Seq)
| PRJNA445739 | ENA
Project description:In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Med23- deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are much easier to be activated in response to physio- logical stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is downregulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of myeloid potential of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid potential of HSCs and HSC activation upon stresses.
2018-07-14 | GSE112008 | GEO
Project description:Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells
| PRJNA438937 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-07-15 | GSE112359 | GEO
Project description:Liver fibrosis, often associated with cirrhosis and hepatocellular carcinomas, is characterized by hepatic damage, an inflammatory response, and hepatic stellate cell (HSC) activation, although the underlying mechanisms are largely unknown.Here,we show that the MED23 subunit of the transcriptional Mediator complex participates in the development of experimental liver fibrosis. Compared with their control littermates, mice with hepatic Med23 deletion exhibited aggravated CCl4-induced liver fibrosis, with enhanced chemokine production and inflammatory infiltration as well as increased hepatocyte regeneration. Mechanistically, the orphan nuclear receptor RORα activates the expression of the liver fibrosis-related chemokines CCL5 and CXCL10, which is suppressed by the Mediator subunit MED23. We further found that the inhibition of Ccl5 and Cxcl10 expression by MED23 likely occurs due to G9a-mediated H3K9 dimethylation of the target promoters. Collectively, these findings reveal hepatic MED23 as a key modulator of chemokine production and inflammatory responses and define the MED23-CCL5/CXCL10 axis as a potential target for clinical intervention in liver fibrosis.
2020-06-06 | GSE137457 | GEO
Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription. We performed an exon array experiment using HeLa cells expressing Med23, hnRNP L or control siRNAs which were established by a virus-mediated siRNA technology. Each sample was done in three biological replicates. Total RNA of these cell lines was processed and hybridized to the Affymetrix human exon array.
2012-02-24 | E-GEOD-33771 | biostudies-arrayexpress
Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription. Examination of hnRNP L and H3K36me3 enrichment in sictrl and si23 Hela cells
2012-02-24 | E-GEOD-33887 | biostudies-arrayexpress