Donnelly Centre, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Donnelly Centre, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Stem Cell Reports. 2024 Nov 12;19(11):1620-1634. doi: 10.1016/j.stemcr.2024.10.003. Epub 2024 Oct 31.
Direct reprogramming involves the conversion of differentiated cell types without returning to an earlier developmental state. Here, we explore how heterogeneity in developmental lineage and maturity of the starting cell population contributes to direct reprogramming using the conversion of murine fibroblasts into neurons. Our hypothesis is that a single lineage of cells contributes to most reprogramming and that a rare elite precursor with intrinsic bias is the source of reprogrammed neurons. We find that nearly all reprogrammed neurons are derived from the neural crest (NC) lineage. Moreover, when rare proliferating NC precursors are selectively ablated, there is a large reduction in the number of reprogrammed neurons. Previous interpretations of this paradigm are that it demonstrates a cell fate conversion across embryonic germ layers (mesoderm to ectoderm). Our interpretation is that this is actually directed differentiation of a neural lineage stem cell in the skin that has intrinsic bias to produce neuronal progeny.
直接重编程涉及到无需回到早期发育状态即可将分化细胞类型转化为另一种类型。在这里，我们使用将小鼠成纤维细胞重编程为神经元的方法，探索了起始细胞群体在发育谱系和成熟度方面的异质性如何影响直接重编程。我们的假设是，单个细胞谱系有助于大多数重编程，而具有内在偏向的稀有精英前体是重编程神经元的来源。我们发现，几乎所有的重编程神经元都来源于神经嵴（NC）谱系。此外，当稀有增殖的 NC 前体被选择性地消除时，重编程神经元的数量会大大减少。以前对这一范例的解释是，它证明了胚胎生殖层（中胚层到外胚层）之间的细胞命运转换。我们的解释是，实际上这是皮肤中的神经谱系干细胞的定向分化，该干细胞具有内在的产生神经元后代的偏向性。
