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

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

PROVIDER: PRJNA476601 | ENA |

REPOSITORIES: ENA

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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

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

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

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

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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).

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Interplay of vascular endothelial growth factor receptors in organ-specific endothelial cell survival

Project description:The aim was to study immediate changes in gene expression of lung and heart endothelial cells after single or compound deletions of vascular endothelial growth factors.

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