Accelerated Differentiation of Human Pluripotent Stem Cells into Neural Lineages via an Early Intermediate Ectoderm Population,STEM CELLS

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Accelerated Differentiation of Human Pluripotent Stem Cells into Neural Lineages via an Early Intermediate Ectoderm Population
STEM CELLS ( IF 4.0 ) Pub Date : 2020-08-19 , DOI: 10.1002/stem.3260
Patrick Walsh _{1,

2} , Vincent Truong _{1,

3} , Sushmita Nayak ₁ , Marietta Saldías Montivero ₄ , Walter C Low _{1,

5} , Ann M Parr _{1,

5} , James R Dutton _{1,

2}

Affiliation

Differentiation of human pluripotent stem cells (hPSCs) into ectoderm provides neurons and glia useful for research, disease modeling, drug discovery, and potential cell therapies. In current protocols, hPSCs are traditionally differentiated into an obligate rostro‐dorsal ectodermal fate expressing PAX6 after 6 to 12 days in vitro when protected from mesendoderm inducers. This rate‐limiting step has performed a long‐standing role in hindering the development of rapid differentiation protocols for ectoderm‐derived cell types, as any protocol requires 6 to 10 days in vitro to simply initiate. Here, we report efficient differentiation of hPSCs into a naive early ectodermal intermediate within 24 hours using combined inhibition of bone morphogenic protein and fibroblast growth factor signaling. The induced population responds immediately to morphogen gradients to upregulate rostro‐caudal neurodevelopmental landmark gene expression in a generally accelerated fashion. This method can serve as a new platform for the development of novel, rapid, and efficient protocols for the manufacture of hPSC‐derived neural lineages.

中文翻译：

通过早期中间外胚层群加速人类多能干细胞分化为神经谱系

人类多能干细胞 (hPSC) 分化为外胚层，可提供神经元和神经胶质细胞，可用于研究、疾病建模、药物发现和潜在的细胞疗法。在目前的方案中，在体外 6 至 12 天后，当受到中内胚层诱导剂的保护时，hPSC 传统上会分化为表达 PAX6 的专性前背侧外胚层命运。这种限速步骤在阻碍外胚层衍生细胞类型快速分化方案的开发方面发挥了长期作用，因为任何方案都需要在体外 6 至 10 天才能简单启动。在这里，我们报告了通过联合抑制骨形态发生蛋白和成纤维细胞生长因子信号传导，hPSC 在 24 小时内有效分化为幼稚的早期外胚层中间体。诱导群体立即对形态发生素梯度做出反应，以普遍加速的方式上调头尾神经发育标志性基因表达。该方法可以作为开发新颖、快速、高效的方案的新平台，用于制造 hPSC 衍生的神经谱系。

更新日期：2020-08-19

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