ETV2は胎児期の造血-血管系の発生に必須の因子である。申請者らは既に分化した体性細胞である成人皮膚線維芽細胞をETV2導入により血管内皮細胞に直接転換できることを報告した。面白いことにETV2発現線維芽細胞は造血分化に必須の転写因子RUNX1, TAL1, GATA2も発現していることを見出した。そこでETV2と共に20種類のhemogenic endothelium特異的転写因子を導入し, SCF, FLT3L, TPO, IL-3, IL-6の存在下でOP9細胞と共培養すると, CD45及びc-Kit陽性の血球様細胞が出現した。本成果より皮膚から血液細胞を作製できる可能性が見出された。
An ETS family transcription factor ETV2 is essential for hemato-endothelial development in embryo. We have reported that human adult skin fibroblasts directly convert into functional endothelial cells by transducing ETV2. Interestingly we found that ETV2-transduced human adult skin fibroblasts also expressed RUNX1, TAL1, and GATA2, which were transcription factors essential for hematopoiesis. Thus to generate hematopoietic cells from fibroblasts, we transduced not only ETV2 but also 20 kinds of transcription factors essential for hematopoiesis into human adult skin fibroblasts, then co-cultured them with OP9 stroma cells in the presence of SCF, FLT3L, TPO, IL-3, and IL-6 for four weeks. Consequently we detected CD45+c-Kit+ hematopoietic-like cells by FACS analysis. Our results may leads to generation of functional hematopoietic cells from individual skin in the future.
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