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。
Direct reprogramming of non-limb fibroblasts to cells with properties of limb progenitors.
机构信息
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Department of Biology, Kyushu University, Fukuoka 819-0395, Japan.
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
出版信息
Dev Cell. 2024 Feb 5;59(3):415-430.e8. doi: 10.1016/j.devcel.2023.12.010.
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.
早期的肢芽由来自侧板中胚层（LPM）的间质肢祖细胞组成。LPM 还产生了侧翼和颈部的中胚层成分。然而，这些其他水平的细胞不能产生在肢中发现的各种细胞类型。利用直接重编程方法，我们发现了一组通常在早期肢芽中表达的因子（Prdm16、Zbtb16 和 Lin28a），它们能够赋予小鼠非肢纤维母细胞肢祖细胞样特性。重编程细胞显示出相似的基因表达谱，并能分化为与内源性肢祖细胞相似的细胞类型。进一步添加 Lin41 可增强重编程细胞的增殖。这些结果表明，这四个相同的因子可能在内源性肢祖细胞的特化中发挥关键作用。
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