CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Ambulatory Surgical Center, The 2nd Clinical medical College (Shenzhen People's Hospital) of Jinan University, The 1st Affiliated Hospitals of Southern University of Science and Technology, Shenzhen, 518020, China.
Sci China Life Sci. 2021 Dec;64(12):2100-2113. doi: 10.1007/s11427-020-1897-0. Epub 2021 Mar 16.
A stable, rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in treating neurological disorders and diseases. Herein, we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells (NPCs) from human ESC/iPSCs on Type I Collagen. The derived cells not only displayed the requisite markers, but also behaved similarly to classic NPCs both in vitro and in vivo. Upon transplantation into traumatic brain injury model, the derived NPCs facilitated recovery from injury. We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen, and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day. Meanwhile, ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction. Totally, our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases' treatment.
建立一种稳定、快速、有效的神经分化方法对于人胚胎干细胞(ESCs)或诱导多能干细胞(iPSCs)在治疗神经紊乱和疾病中的临床应用至关重要。在此,我们建立了一种新型且强大的单层分化方法,可在 I 型胶原上从人 ESC/iPSC 产生功能性神经祖细胞(NPC)。所得到的细胞不仅显示出所需的标志物,而且在体外和体内与经典 NPC 表现相似。在移植到创伤性脑损伤模型后,衍生的 NPC 有助于从损伤中恢复。我们还发现,在 I 型胶原上的整个分化过程中 SMAD 信号一直保持下调,并且多能信号随着第三天神经早期标志物的上调而迅速下调。同时,ATAC-seq 数据显示,在 NPC 诱导过程中,不同的转录组和全基因组染色质动力学存在相关的介导作用。总的来说,我们的结果为从人 ESC/iPSC 产生用于神经疾病治疗的 NPC 提供了一种便捷的方法。