- 作者: Jie Zheng, Wonjin Yun, Junghyun Park, Phil Jun Kang, Gilju Lee, Gwonhwa Song, In Yong Kim and Seungkwon You
- 作者服務機構: 1. Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea 2. Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea 3. Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 08308, Republic of Korea
- 中文摘要:
- 英文摘要:
Background
Human keratinocytes and derived products are crucial for skin repair and regeneration. Despite substantial advances in engineered skin equivalents, their poor availability and immunorejection remain major challenges in skin grafting.
Methods
Induced keratinocyte-like cells (iKCs) were directly reprogrammed from human urine cells by retroviral transduction of two lineage-specific transcription factors BMI1 and △NP63α (BN). Expression of keratinocyte stem cell or their differentiation markers were assessed by PCR, immunofluorescence and RNA-Sequencing. Regeneration capacity of iKCs were assessed by reconstitution of a human skin equivalent under air-interface condition.
Results
BN-driven iKCs were similar to primary keratinocytes (pKCs) in terms of their morphology, protein expression, differentiation potential, and global gene expression. Moreover, BN-iKCs self-assembled to form stratified skin equivalents in vitro.
Conclusions
This study demonstrated an approach to generate human iKCs that could be directly reprogrammed from human somatic cells and extensively expanded in serum- and feeder cell-free systems, which will facilitate their broad applicability in an efficient and patient-specific manner. - 中文關鍵字:
- 英文關鍵字: Induced keratinocyte-like cells, Urine cells, Direct lineage reprogramming, Long-term expansion, Skin reconstitution