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通过特定因子将成纤维细胞直接重编程为脂肪生成、神经生成和肝生成分化谱系。

Directly reprogramming fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by defined factors.

作者信息

Wu Wei, Jin Yu-Qing, Gao Zhen

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.

Department of Plastic and Reconstructive Surgery, Shanghai General Hospital, Shanghai 200080, P.R. China.

出版信息

Exp Ther Med. 2017 Jun;13(6):2685-2690. doi: 10.3892/etm.2017.4365. Epub 2017 Apr 20.

DOI:10.3892/etm.2017.4365
PMID:28587331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5450766/
Abstract

The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types represents a great potential technology for regenerative medicine. In the present study, the potential of key developmental adipogenic, neurogenic and hepatogenic regulators to reprogram human fibroblasts into adipocytes, neurocytes and hepatocytes was investigated. The results demonstrated that direct reprogramming of octamer-binding transcription factor 4 (Oct4) and CCAAT-enhancer-binding protein (C/EBP)β activated C/EBPα and peroxisome proliferator-activated receptor-γ expression, inducing the conversion of fibroblasts into adipocytes. Similarly, direct reprogramming of the transcription factors sex determining region-box 2, trans-acting T-cell specific transcription factor (GATA-3) and neurogenic differentiation 1 in fibroblasts may induce neurogenic differentiation through hemagglutinating virus of Japan envelope (HVJ-E) transfection. Moreover, hepatogenic differentiation was induced by combining the direct reprogramming of Oct4, GATA-3, hepatocyte nuclear factor 1 homeobox α and forkhead box protein A2 in fibroblasts. These results demonstrate that specific transcription factors and reprogramming factors are able to directly reprogram fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by HVJ-E transfection.

摘要

将成体细胞重编程为多能细胞或直接重编程为其他成体细胞类型,是再生医学中一项极具潜力的技术。在本研究中,研究了关键发育性脂肪生成、神经生成和肝生成调节因子将人成纤维细胞重编程为脂肪细胞、神经细胞和肝细胞的潜力。结果表明,八聚体结合转录因子4(Oct4)和CCAAT增强子结合蛋白(C/EBP)β的直接重编程激活了C/EBPα和过氧化物酶体增殖物激活受体-γ的表达,诱导成纤维细胞转化为脂肪细胞。同样,成纤维细胞中转录因子性别决定区框2、反式作用T细胞特异性转录因子(GATA-3)和神经生成分化因子1的直接重编程可能通过日本血凝病毒包膜(HVJ-E)转染诱导神经生成分化。此外,通过将成纤维细胞中Oct4、GATA-3、肝细胞核因子1同源框α和叉头框蛋白A2的直接重编程相结合,诱导了肝生成分化。这些结果表明,特定转录因子和重编程因子能够通过HVJ-E转染将成纤维细胞直接重编程为脂肪生成、神经生成和肝生成分化谱系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/08d217c3c3cf/etm-13-06-2685-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/0e314a0b4da6/etm-13-06-2685-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/1e25ddbb0c5a/etm-13-06-2685-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/b4955910ae0e/etm-13-06-2685-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/277afc3b9c7a/etm-13-06-2685-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/08d217c3c3cf/etm-13-06-2685-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/0e314a0b4da6/etm-13-06-2685-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/1e25ddbb0c5a/etm-13-06-2685-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/b4955910ae0e/etm-13-06-2685-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/277afc3b9c7a/etm-13-06-2685-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b3/5450766/08d217c3c3cf/etm-13-06-2685-g04.jpg

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