Direct reprogramming of non-limb fibroblasts to cells with properties of limb progenitors

将非肢体成纤维细胞直接重编程为具有肢体祖细胞特性的细胞

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作者:Yuji Atsuta ,ChangHee Lee ,Alan R Rodrigues ,Charlotte Colle ,Reiko R Tomizawa ,Ernesto G Lujan ,Patrick Tschopp ,Laura Galan ,Meng Zhu ,Joshua M Gorham ,Jean-Pierre Vannier ,Christine E Seidman ,Jonathan G Seidman ,Marian A Ros ,Olivier Pourquié ,Clifford J Tabin

Abstract

The early limb bud consists of mesenchymal limb progenitors derived from the lateral plate mesoderm (LPM). The LPM also gives rise to the mesodermal components of the flank and neck. However, the cells at these other levels cannot produce the variety of cell types found in the limb. Taking advantage of a direct reprogramming approach, we find a set of factors (Prdm16, Zbtb16, and Lin28a) normally expressed in the early limb bud and capable of imparting limb progenitor-like properties to mouse non-limb fibroblasts. The reprogrammed cells show similar gene expression profiles and can differentiate into similar cell types as endogenous limb progenitors. The further addition of Lin41 potentiates the proliferation of the reprogrammed cells. These results suggest that these same four factors may play pivotal roles in the specification of endogenous limb progenitors. Keywords: Lin28a; Lin41; Pdrm16; Zbtb16; lateral plate mesoderm; limb bud; limb culture; limb progenitors; reprogramming.

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