Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors
Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors
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DOI：
10.1101/2021.10.01.462632
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发表时间：
2021-10
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通讯作者：
Y. Atsuta;Changhee Lee;Alan R Rodrigues;Charlotte Colle;Reiko R. Tomizawa;Ernesto Lujan;P. Tschopp;Joshua M. Gorham;J. Vannier;C. Seidman;J. Seidman;O. Pourquié;C. Tabin
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文献类型：
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作者：
Y. Atsuta;Changhee Lee;Alan R Rodrigues;Charlotte Colle;Reiko R. Tomizawa;Ernesto Lujan;P. Tschopp;Joshua M. Gorham;J. Vannier;C. Seidman;J. Seidman;O. Pourquié;C. Tabin
早期肢芽由来自侧板中胚层(LPM)的间充质祖细胞(肢祖细胞)组成，LPM产生成熟肢芽的大部分组织。LPM还形成躯干、侧翼和颈部的中胚层成分。然而，在这些其他轴向水平上产生的间充质细胞不能产生在肢芽中发现的各种细胞类型，也不能被引导形成图案化的附属器样结构，即使当放置在负责组织肢芽的信号的背景下时也是如此。在这里，通过利用直接重新编程的方法，我们发现了一组在早期肢芽中正常表达的因子(Prdm16、Zbtb16和Lin28)，它们能够向非肢体成纤维细胞赋予肢体祖细胞样属性。被这些因子重新编程的细胞表现出相似的基因表达谱，并可以分化为类似的细胞类型，作为内源性肢体祖细胞。进一步加入LIN41可促进重编程细胞的增殖，同时抑制分化。这些结果表明，这四个关键因素可能在内源性肢体祖细胞的指定中发挥关键作用。
The early limb bud consists of mesenchymal progenitors (limb progenitors) derived from the lateral plate mesoderm (LPM) that produce most of the tissues of the mature limb bud. The LPM also gives rise to the mesodermal components of the trunk, flank and neck. However, the mesenchymal cells generated at these other axial levels cannot produce the variety of cell types found in the limb bud, nor can they be directed to form a patterned appendage-like structure, even when placed in the context of the signals responsible for organizing the limb bud. Here, by taking advantage of a direct reprogramming approach, we find a set of factors (Prdm16, Zbtb16, and Lin28) normally expressed in the early limb bud, that are capable of imparting limb progenitor-like properties to non-limb fibroblasts. Cells reprogrammed by these factors show similar gene expression profiles, and can differentiate into similar cell types, as endogenous limb progenitors. The further addition of Lin41 potentiates proliferation of the reprogrammed cells while suppressing differentiation. These results suggest that these same four key factors may play pivotal roles in the specification of endogenous limb progenitors.