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Defined Physicochemical Cues Steering Direct Neuronal Reprogramming on Colloidal Self- Assembled Patterns (cSAPs)

Journal: ACS Nano

Authors: Harati, Javad; Liu, Kun; Shahsavarani, Hosein; Du, Ping; Galluzzi, Massimiliano; Deng, Ke; Mei, Jei; Chen, Hsien-Yeh; Bonakdar, Shahin; Aflatoonian, Behrouz; Hou, Guoqiang; Zhu, Yingjie; Pan, Haobo; Wong, Raymond C. B.; Shokrgozar, Mohammad Ali; Song, Weihong; Wang, Peng-Yuan

Organizations: Ministry of Science and Technology of China [2019YFE0113000, 2022YFA1105101]; National Natural and Science Foundation of China [31870988]; Chinese Academy of Sciences [172644KYSB20200002, 172644KYSB20200048]; Department of Science and Technology of Guangdong Province [2021A0505030055]; Zhejiang Provincial Natural Science Foundation of China [LZ23C070004]; Science, Technology, and Innovation Commission of Shenzhen Municipality [GJHZ20180928115804736, ZDSYS20190902093409851]; Pasteur Institute of Iran

Keywords: induced neurons; biophysical cues; neuron subtypes; transdifferentiation; epigenetic status

Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the in vitro microenvironment are potent modulators in the cell fate decision; thus, the present study explores the effects of a customized pattern (named colloidal self-assembled patterns, cSAPs) on iN generation from human fibroblasts using small molecules. The result revealed that the cSAP, composed of binary particles in a hexagonal-close-packed (hcp) geometry, is capable of improving neuronal reprogramming efficiency and steering the ratio of the iN subtypes. Cells exhibited distinct cell morphology, upregulated cell adhesion markers (i.e., SDC1 and ITGAV), enriched signaling pathways (i.e., Hippo and Wnt), and chromatin remodeling on the cSAP compared to those on the control substrates. The result also showed that the iN subtype specification on cSAP was surface-dependent; therefore, the defined physicochemical cue from each cSAP is exclusive. Our findings show that direct cell reprogramming can be manipulated through specific biophysical cues on the artificial matrix, which is significant in cell transdifferentiation and lineage conversion.