Neural crest precursors from the skin are the primary source of directly reprogrammed neurons.

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-31 DOI:10.1016/j.stemcr.2024.10.003
Justin J Belair-Hickey, Ahmed Fahmy, Wenbo Zhang, Rifat S Sajid, Brenda L K Coles, Michael W Salter, Derek van der Kooy
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Abstract

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.

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来自皮肤的神经嵴前体是直接重编程神经元的主要来源。
直接重编程涉及已分化细胞类型的转换,而无需回到早期的发育状态。在这里,我们通过将小鼠成纤维细胞转化为神经元的实验,探讨了起始细胞群在发育谱系和成熟度方面的异质性是如何促进直接重编程的。我们的假设是,单系细胞促成了大多数重编程,而具有内在偏向性的稀有精英前体是重编程神经元的来源。我们发现,几乎所有重编程神经元都来自神经嵴(NC)系。此外,当选择性地消减稀有增殖的 NC 前体时,重编程神经元的数量会大幅减少。以往对这一范例的解释是,它展示了胚胎胚层(中胚层到外胚层)之间的细胞命运转换。我们的解释是,这实际上是皮肤中神经系干细胞的定向分化,其内在偏向于产生神经元后代。
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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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