Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The RNA m6A binding protein YTHDF2 promotes the B cell to plasma cell transition

ABSTRACT: The B cell to plasma cell transition relies on the coordinated remodelling of the gene expression program. We performed a CRISPR/Cas9 knockout screen of RNA binding proteins to identify post-transcriptional regulation of gene expression during the B cell terminal differentiation. The m6A binding protein YTHDF2 was identified as promoting B cell terminal differentiation. In the absence of YTHDF2 the germinal centre reaction is broadly intact, however, plasma cells fail to accumulate. YTHDF2 has previously been shown to mediate RNA decay through the recruitment of the CCR4-NOT deadenylase machinery. Furthermore, our genetic screen in B cells identified that other CCR4-NOT recruitment factors inhibit rather than promote differentiation. Thus, the CCR4-NOT complex coordinates competing regulatory pathways of B cell differentiation at the post-transcriptional level.

ORGANISM(S): Mus musculus

PROVIDER: GSE179919 | GEO | 2021/07/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

YTHDF2/3 are required for somatic reprogramming through different RNA deadenylation pathways

Project description:N6-methyladenosine (m6A), the most abundant reversible modification on eukaryote messenger RNA, is recognized by a series of readers, including the YT521-B homology domain family (YTHDF) proteins, which are coupled to perform physiological functions. Here, we report that YTHDF2 and YTHDF3, but not YTHDF1, are required for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Mechanistically, we found that YTHDF3 recruits the PAN2-PAN3 deadenylase complex and conduces to reprogramming by promoting mRNA clearance of somatic genes, including Tead2 and Tgfb1, which parallels the activity of the YTHDF2-CCR4-NOT deadenylase complex. Ythdf2/3 deficiency further represses mesenchymal-to-epithelial transition (MET) and chromatin silencing at loci containing the TEAD motif, contributing to decreased reprogramming efficiency. Moreover, RNA interference of Tgfb1 or the Hippo signaling effectors Yap1, Taz, and Tead2 rescues Ythdf2/3-defective reprogramming. Overall, YTHDF2/3 couple RNA deadenylation and regulation with the clearance of somatic genes provides insights into iPSC reprogramming at the posttranscriptional level.

2020-08-19 | GSE156437 | GEO

Microarray profiling of YTHDF2 deficient mouse oocytes

Project description:To study the role of the protein YTHDF2 during female gametogenesis, its gene was conditionally deleted in oocytes. Total RNA samples from YTHDF2 deficient GV and MII oocytes (and control oocytes) were subjected to array profiling.

2018-02-12 | E-MTAB-5576 | biostudies-arrayexpress

Microarray analysis of YTHDF2-deficient leukemic stem cells

Project description:YTHDF2 is overexpressed in a broad spectrum of human acute myeloid leukemias (AML). To study the role of YTHDF2 in leukemia, total RNA from Ythdf2CKO (n=4) and Ythdf2CTL (n=4) leukemic stem cells were used for Affymetrix global gene expression analysis.

2019-04-05 | E-MTAB-7782 | biostudies-arrayexpress

The RNA m6A reader YTHDF2 controls NK cell anti-tumor and anti-viral immunity

Project description:N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification on RNA. NK cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. However, whether and how m6A modifications affect NK cell immunity remains unknown. Here, we discover that YTHDF2, a well-known m6A reader, is upregulated in NK cells upon activation by cytokines, tumors, and cytomegalovirus infection. Ythdf2 deficiency in NK cells impairs NK cell anti-tumor and anti-viral activity in vivo. YTHDF2 maintains NK cell homeostasis and terminal maturation, correlating with modulating NK cell trafficking and regulating Eomes, respectively. YTHDF2 promotes NK cell effector function and is required for IL-15-mediated NK cell survival and proliferation by forming a STAT5-YTHDF2 positive feedback loop. Transcriptome-wide screening identifies Tardbp to be involved in cell proliferation or survival as a YTHDF2-binding target in NK cells. Collectively, we elucidate the biological roles of m6A modifications in NK cells and highlight a new direction to harness NK cell anti-tumor immunity.

2021-05-08 | GSE174027 | GEO

The tumor intrinsic role of the m6A reader YTHDF2 in regulating immune evasion [scRNA-seq]

Project description:Tumors evade attacks from the immune system through various mechanisms. Here, we identify a component of tumor immune evasion mediated by YTH domain-containing family protein 2 (YTHDF2), a reader protein that usually destabilizes m6A-modified mRNA. Loss of tumoral YTHDF2 inhibits tumor growth and prolongs survival in immunocompetent tumor models. Mechanistically, tumoral YTHDF2 deficiency promotes the recruitment of macrophages via CX3CL1 and enhances mitochondrial respiration of CD8+ T cells by impairing tumor glycolysis metabolism. Tumoral YTHDF2 deficiency promotes inflammatory macrophage polarization and antigen presentation in the presence of IFN-γ. In addition, IFN-γ induces autophagic degradation of tumoral YTHDF2, thereby sensitizing tumor cells to CD8+ T cell-mediated cytotoxicity. Last, we identified a small molecule compound that preferentially induces YTHDF2 degradation, which shows a potent antitumor effect alone but a better effect when combined with anti-PD-L1 or anti-PD-1 antibodies. Collectively, YTHDF2 appears to be a tumor-intrinsic regulator that orchestrates immune evasion, representing a promising target for enhancing cancer immunotherapy.

2024-05-31 | GSE239426 | GEO

The tumor intrinsic role of the m6A reader YTHDF2 in regulating immune evasion [RNA-seq]

2024-05-31 | GSE239423 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [MeRIP-Seq]

Project description:RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.

2023-04-28 | GSE206384 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [CITE-Seq]

2023-04-28 | GSE206381 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [RIP-Seq]

2023-04-28 | GSE206379 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [scRNA-Seq]

2023-04-28 | GSE206378 | GEO