Department of Molecular Biology & CMBI, Genomics, Stem Cell & Regenerative Medicine Group, University of Innsbruck, Technikerstraße 25, 6020, Innsbruck, Austria.
Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria.
Stem Cell Rev Rep. 2024 Jul;20(5):1325-1339. doi: 10.1007/s12015-024-10698-3. Epub 2024 Mar 22.
Similar to induced pluripotent cells (iPSCs), induced neural stem cells (iNSCs) can be directly converted from human somatic cells such as dermal fibroblasts and peripheral blood monocytes. While previous studies have demonstrated the resemblance of iNSCs to neural stem cells derived from primary sources and embryonic stem cells, respectively, a comprehensive analysis of the correlation between iNSCs and their physiological counterparts remained to be investigated.
Nowadays, single-cell sequencing technologies provide unique opportunities for in-depth cellular benchmarking of complex cell populations. Our study involves the comprehensive profiling of converted human iNSCs at a single-cell transcriptomic level, alongside conventional methods, like flow cytometry and immunofluorescence stainings.
Our results show that the iNSC conversion yields a homogeneous cell population expressing bona fide neural stem cell markers. Extracting transcriptomic signatures from published single cell transcriptomic atlas data and comparison to the iNSC transcriptome reveals resemblance to embryonic neuroepithelial cells of early neurodevelopmental stages observed in vivo at 5 weeks of development.
Our data underscore the physiological relevance of directly converted iNSCs, making them a valuable in vitro system for modeling human central nervous system development and establishing translational applications in cell therapy and compound screening.
类似于诱导多能干细胞（iPSCs），诱导神经干细胞（iNSCs）可直接从人体细胞（如皮肤成纤维细胞和外周血单核细胞）中转化而来。虽然先前的研究已经证明了 iNSCs 分别类似于源自原代来源的神经干细胞和胚胎干细胞，但仍需要对 iNSCs 与它们的生理对应物之间的相关性进行全面分析。
如今，单细胞测序技术为深入研究复杂细胞群体提供了独特的机会。我们的研究涉及在单细胞转录组水平上对转化的人 iNSCs 进行全面分析，同时还采用了流式细胞术和免疫荧光染色等传统方法。
我们的结果表明，iNSC 转化产生了表达真正神经干细胞标志物的同质细胞群体。从已发表的单细胞转录组图谱数据中提取转录组特征，并与 iNSC 转录组进行比较，结果显示与体内发育 5 周时观察到的早期神经发育阶段的胚胎神经上皮细胞具有相似性。
我们的数据强调了直接转化的 iNSCs 的生理相关性，使它们成为模拟人类中枢神经系统发育的有价值的体外系统，并在细胞治疗和化合物筛选中建立转化应用。
