312: Mfsd2a transports LPC to maintain epidermal linoleate pools and desquamation

Wong BHH et al., Proc. Natl. Acad. Sci. U.S.A - Mouse and human studies show the LPC transporter Mfsd2a enables plasma-derived LPC uptake into keratinocytes, preserving linoleate-rich phosphatidylcholine pools and promoting epidermal differentiation. Key terms: Mfsd2a, lysophosphatidylcholine, keratinocyte differentiation, linoleic acid, lipidomics.

Study Highlights:
Using epidermis-specific (2aEpKO) and conventional (2aKO) Mfsd2a-deficient mice, lineage tracing, untargeted shotgun lipidomics, LightOx-LPC uptake assays, and primary human keratinocyte cultures, the authors mapped Mfsd2a expression to suprabasal/granular keratinocytes and demonstrated Mfsd2a-dependent uptake of plasma-derived LPC in vivo. Lipidomic quantification showed reductions in linoleate-containing phospholipids (PL-18:2 decreased ~15% in 2aEpKO and ~13% in 2aKO) and a marked loss of TAG-18:2 (−79% in 2aEpKO). Inducible epidermal Mfsd2a loss produced transient dermatitis, defective desquamation, retained lamellar bodies, and keratinocyte activation, while MFSD2A knockdown in human keratinocytes reduced LPC-driven differentiation. Functional rescue experiments in vitro revealed that LPC-18:1 and LPC-18:2 promote keratinocyte differentiation in an MFSD2A-dependent manner, linking plasma LPC uptake to epidermal lipid homeostasis and differentiation.

Conclusion:
Mfsd2a mediates uptake of plasma-derived LPC (notably LPC-18:2) into suprabasal keratinocytes to maintain linoleate-containing phospholipid pools and support keratinocyte differentiation and normal desquamation.

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Article title:
Mfsd2a is important for maintaining epidermal homeostasis

First author:
Wong BHH

Journal:
Proc. Natl. Acad. Sci. U.S.A

DOI:
10.1073/pnas.2531159123

Reference:
Wong BHH, Behmoaras J, Chua AWC, Galam DLA, Tan BC, Torta F, Chin CF, Mishra K, Ding M, Silver DL. Mfsd2a is important for maintaining epidermal homeostasis. Proc. Natl. Acad. Sci. U.S.A. 2026 Feb 19;123(8):e2531159123. https://doi.org/10.1073/pnas.2531159123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/mfsd2a-lpc-epidermal-homeostasis

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-03-09.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing MFSD2A expression in epidermal keratinocytes, inducible epidermis-specific and conventional Mfsd2a knockout phenotypes, epidermal lipidomics (18:2 species and DAG shifts), LightOx-LPC uptake demonstrating MFSD2A dependence, and MFSD2A-dependent differentiation of human keratin
- transcript topics: MFSD2A expression in differentiated epidermal keratinocytes; Inducible postnatal Mfsd2a deficiency and dermatitis; Conventional Mfsd2a knockout and desquamation defects; Epidermal lipidomics: PL-18:2 and TAG-18:2 reductions; DAG shifts; LPC uptake into epidermis using LightOx-LPC and MFSD2A dependence; MFSD2A-dependent differentiation of human keratinocytes with LPCs

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

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