Version 2 2023-01-03, 15:39Version 2 2023-01-03, 15:39
Version 1 2022-12-30, 11:33Version 1 2022-12-30, 11:33
journal contribution
posted on 2023-01-03, 15:39authored byJavad Harati, Kun Liu, Hosein Shahsavarani, Ping Du, Massimiliano Galluzzi, Ke Deng, Jei Mei, Hsien-Yeh Chen, Shahin Bonakdar, Behrouz Aflatoonian, Guoqiang Hou, Yingjie Zhu, Haobo Pan, Raymond C. B. Wong, Mohammad Ali Shokrgozar, Weihong Song, Peng-Yuan Wang
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.