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Overproduced glycerophosholipids, including phosphocholine (PC), phosphoethanolamine (PE) and phosposerine (PS), in Fanca−/− and Fancd2−/− MSCs may act as ligands to activate Tlr4 receptor in co-cultured WT HSC. Tlr4 in turn signals through MyD88 to activate an NF-kB transcriptional program that leads to upregulation of myeloid-specific gene expression and consequently abnormal myeloid differentiation.
