细胞生物学
生态位
收缩性
肌动蛋白
细胞骨架
转录因子
核心
生物
化学
细胞
基因
生物化学
生态学
内分泌学
栖息地
作者
Kesi Shi,Chengzhen Liang,Xianpeng Huang,Shaoke Wang,Jiangjie Chen,Feng Cao,Chenggui Wang,Liwei Ying,Zhaoqi Pan,Yuang Zhang,Jiawei Shu,Baoyu Yang,Jingkai Wang,Kaishun Xia,Xiaopeng Zhou,Hao Li,Fangcai Li,Yiqing Tao,Qixin Chen
标识
DOI:10.1002/adhm.202201824
摘要
Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs). Next, tunable physical properties of collagen niches are fabricated based on various crosslinking degrees. Collagen niches significantly affect actomyosin cytoskeleton and then influence the maturation of iNPLCs. Using gain- and loss of function approaches, the appropriate physical states of collagen niches are found to significantly enhance the maturation of iNPLCs through actomyosin contractility. Moreover, in a rat model of degenerative disc diseases, iNPLCs with collagen niches are transplanted into the lesion to achieve significant improvements. As a result, overexpression of transcription factors in human dermal fibroblasts are efficiently converted into iNPLCs and the optimal collagen niches affect cellular cytoskeleton and then facilitate iNPLCs maturation toward human nucleus pulposus cells. These findings encourage more in-depth studies toward the interactions of niches and direct conversion, which would contribute to the development of direct conversion.
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