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Dynamics of m6A RNA methylome during leukemogenesis reveals a role of PRMT6-MFSD2A signaling axis in maintaining AML stem cells.[RIP-seq]

ABSTRACT: We delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development, and identify PRMT6, regulated by IGF2BP2, acting as a key for leukemia stem cell maintenance by restraining MFSD2A expression and docosahexaenoic acid level.

ORGANISM(S): Mus musculus

PROVIDER: GSE218610 | GEO | 2023/06/20

REPOSITORIES: GEO

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Dynamics of m6A RNA methylome during leukemogenesis reveals a role of PRMT6-MFSD2A signaling axis in maintaining AML stem cells.[Chip-seq]

Project description:We delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development, and identify PRMT6, regulated by IGF2BP2, acting as a key for leukemia stem cell maintenance by restraining MFSD2A expression and docosahexaenoic acid level.

2023-06-20 | GSE218609 | GEO

Dynamics of m6A RNA methylome during leukemogenesis reveals a role of IGF2BP2-PRMT6-MFSD2A signaling axis in maintaining AML stem cells [Prmt6 RNA-seq]

Project description:Our data reveal that RNA m6A displays a sharp transition during leukemogenesis and involves in acquiring stem cell properties of leukemia stem cells (LSCs). We find that m6A reader IGF2BP2 and protein arginine methyltransferase PRMT6 play key roles in the acquisition of LSCs properties. Genetical deletion and pharmacological inhibition of PRMT6 delayed AML development. Mechanistically, IGF2BP2 regulates PRMT6 expression by stabilizing its mRNA in an m6A-dependent manner. PRMT6 further suppresses the expression of lipid transporter MFSD2A by establishing inactive H3R2me2a in its promoter region. Loss of PRMT6 and IGF2BP2 upregulates the expression of MFSD2A that increases the uptake of docosahexaenoic acid. Collectively, our findings uncover a critical role of IGF2BP2-PRMT6-MFSD2A signaling axis in AML development, and provide a promising therapeutic strategy for targeting LSCs.

2023-06-20 | GSE210279 | GEO

Dynamics of m6A RNA methylome during leukemogenesis reveals a role of IGF2BP2-PRMT6-MFSD2A signaling axis in maintaining AML stem cells [MeRIP-seq]

2023-06-20 | GSE210280 | GEO

Dynamics of m6A RNA methylome during leukemogenesis reveals a role of IGF2BP2-PRMT6-MFSD2A signaling axis in maintaining AML stem cells [IGF2BP2 RNA-seq]

2023-06-20 | GSE210278 | GEO

Impact of Major Facilitator Superfamily Domain containing 2a (Mfsd2a) mediated lipid transport on oligodendrocyte lineage development at single cell level.

Project description:Mfsd2a is involved in transport of essential fatty acids such as docosahexaenoic acid (DHA) from the periphery across blood brain barrier (BBB) into the brain parenchyma. Loss of Mfsd2a in humans leads to microcephaly and hypomyelination. The significance of lipid species transported by Mfsd2a on oligodendrocyte lineage development is not known. Using OPC specific deletion of Mfsd2a (2aOKO) in mice we found that OPC cell state, differentiation and oligodendrocytes maturation is disrupted resulting in hypomyelination compared to 2afl/fl controls. Single cell RNAsequencing analysis was performed on total oligodendrocyte population from postnatal mouse brain using Ribo-TRAP mouse lines that labels complete oligodendrocyte lineage with GFP fluorescence to understand the influence of Mfsd2a on oligodendrocyte development.

2023-05-17 | GSE211879 | GEO

Transcriptional changes in oligodendrocyte precursor cells (OPC) and immature oligodendrocytes (O4) of postnatal mouse brain due to Major Facilitator Superfamily Domain containing 2a (Mfsd2a) mediated lipid transport.

Project description:Mfsd2a plays an important role in accretion of essential fatty acids such as docosahexaenoic acid (DHA) from the periphery into the brain. Loss of Mfsd2a in humans leads to microcephaly and hypomyelination. The precise impact of lipid species transported by Mfsd2a on myelination is not known. Using OPC specific deletion of Mfsd2a (2aOKO) in mice we found that OPC cell state, differentiation and oligodendrocytes maturation is disrupted resulting in hypomyelination. RNAsequencing and differential gene expression analysis was performed on OPC and O4 cells from postnatal mouse brain to understand the influence of Mfsd2a on oligodendrocyte development.

2023-05-17 | GSE211228 | GEO

Comparison of wild-type and Mfsd2a KO eye cups

Project description:Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the omega-3 fatty acid docosahexaenote (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier (BRB) or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine symporter expressed at the BRB. Microarrays were used to determine difference in gene expression between wild-type and Mfsd2a KO eye cups. RNA was extracted from eye cups from postnatal day 13 wild-type and Mfsd2a KO mice. Equal amounts of RNA from 6 wild-type eye cups were pooled for the wild-type sample, or 6 Mfsd2a KO eye cups were pooled for the Mfsd2a KO sample. Microarray profiling was done on pooled samples with a RIN cut-off of 7.0 using Mouse 430 2.0 arrays (Affymetrix).

2016-03-23 | E-GEOD-77403 | biostudies-arrayexpress

Study of vascular endothelial-specific and inducible vascular endothelial-specific deletion of Major Facilitator Superfamily Domain containing 2a (Mfsd2a) in mice.

Project description:Brain development requires a massive increase in brain lipogenesis and accretion of the essential omega-3 fatty acid docosahexaenoic acid (DHA). Brain acquisition of DHA is primarily mediated by the transporter Major Facilitator Superfamily Domain containing 2a (Mfsd2a) expressed in the endothelium of the blood-brain barrier. Mfsd2a transports DHA and other polyunsaturated fatty acids esterified to lysophosphatidylcholine (LPC-DHA). However, the function of Mfsd2a and DHA in brain development is incompletely understood. Using vascular endothelial-specific (2aECKO) and inducible vascular endothelial-specific (2aiECKO) deletion of Mfsd2a in mice, we found Mfsd2a to be uniquely required postnatally at the blood-brain barrier for normal brain growth and DHA accretion, with DHA deficiency preceding the onset of microcephaly. Gene expression profiling analysis of these DHA deficient brains indicated that Srebp-1 and Srebp-2 pathways were highly elevated. Affymetrix gene arrays were used to determine differences in gene expression between 2aECKO or 2aiECKO relative to their respective controls in the developing brain.

2018-07-11 | GSE115971 | GEO

Identification of interaction partners of PRMT6

Project description:To identify transcription factors of PRMT6 which could recruit PRMT6 to target genes, we used affinity purification of avi-tagged PRMT6 in combination with stable isotope labeling of amino acids in cell culture (SILAC) based mass spectrometry. For this, K562 cells were transduced with a lentiviral co expression vector for the BirA-ligase and avi-PRMT6 with a 21 amino acid taq, which is biotinylated in the cells. Cells expressing the BirA-ligase only served as a control. Avi-PRMT6 cells were grown in heavy SILAC medium and control cells in light SILAC medium for seven passages. Nuclear extracts were prepared from 1x108 cells and subjected to avi-PRMT6 affinity purification using magnetic streptavidin beads. Subsequently, the proteins were eluted from the beads. The eluates from the avi-PRMT6 and the control were mixed in a one to one ratio. Subsequently, we performed quantitative mass spectrometry (MS)-based analysis of the PRMT6 interactome.

2021-09-09 | PXD021804 | Pride

PRMT6 knockdown effects on the early zebrafish development

Project description:Zygotic genome activation (ZGA), which is according to the midblastula transition in zebrafish, is an important event during the maternal-zygotic transition in animals. Our preliminary study and other groupâs works indicate that epigenetic regulations play an essential role in ZGA. Morpholino was employed to knockdown PRMT6. We used microarrays to analyze the global gene expression in prmt6 morphants. prmt6 MO (0.3mM) was injected into the one-two cell zebrafish, prmt6 cMO (0.3mM) injection as a control. At 6 hpf, embryos were classified into three subtypes (normal, mild and severe) and prepared for global gene expression analysis with Affymetrix Zebrafish Genome Arrays. The severe subtype and the control were repeated three times.

2015-11-25 | E-GEOD-63735 | biostudies-arrayexpress

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