Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors
Recent studies using defined transcription factors to convert skin fibroblasts into chondrocytes have raised the question of whether osteo-chondroprogenitors expressing SOX9 and RUNX2 could also be generated during the course of the reprogramming process. Here, we demonstrated that doxycycline-induc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117301728 |
| _version_ | 1811267803454373888 |
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| author | Yinxiang Wang Ming-Hoi Wu May Pui Lai Cheung Mai Har Sham Haruhiko Akiyama Danny Chan Kathryn S.E. Cheah Martin Cheung |
| author_facet | Yinxiang Wang Ming-Hoi Wu May Pui Lai Cheung Mai Har Sham Haruhiko Akiyama Danny Chan Kathryn S.E. Cheah Martin Cheung |
| author_sort | Yinxiang Wang |
| collection | DOAJ |
| description | Recent studies using defined transcription factors to convert skin fibroblasts into chondrocytes have raised the question of whether osteo-chondroprogenitors expressing SOX9 and RUNX2 could also be generated during the course of the reprogramming process. Here, we demonstrated that doxycycline-inducible expression of reprogramming factors (KLF4 [K] and c-MYC [M]) for 6 days were sufficient to convert murine fibroblasts into SOX9+/RUNX2+ cellular aggregates and together with SOX9 (S) promoted the conversion efficiency when cultured in a defined stem cell medium, mTeSR. KMS-reprogrammed cells possess gene expression profiles akin to those of native osteo-chondroprogenitors with elevated osteogenic properties and can differentiate into osteoblasts and chondrocytes in vitro, but form bone tissue upon transplantation under the skin and in the fracture site of mouse tibia. Altogether, we provide a reprogramming strategy to enable efficient derivation of osteo-chondrogenic cells that may hold promise for cell replacement therapy not limited to cartilage but also for bone tissues. |
| first_indexed | 2024-04-12T21:09:20Z |
| format | Article |
| id | doaj.art-535f352bded743a88c4fbc69326b7d1f |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-12T21:09:20Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-535f352bded743a88c4fbc69326b7d1f2022-12-22T03:16:37ZengElsevierStem Cell Reports2213-67112017-06-01861587159910.1016/j.stemcr.2017.04.018Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription FactorsYinxiang Wang0Ming-Hoi Wu1May Pui Lai Cheung2Mai Har Sham3Haruhiko Akiyama4Danny Chan5Kathryn S.E. Cheah6Martin Cheung7Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Orthopedic Surgery, Gifu University, Gifu 501-1194, JapanDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaRecent studies using defined transcription factors to convert skin fibroblasts into chondrocytes have raised the question of whether osteo-chondroprogenitors expressing SOX9 and RUNX2 could also be generated during the course of the reprogramming process. Here, we demonstrated that doxycycline-inducible expression of reprogramming factors (KLF4 [K] and c-MYC [M]) for 6 days were sufficient to convert murine fibroblasts into SOX9+/RUNX2+ cellular aggregates and together with SOX9 (S) promoted the conversion efficiency when cultured in a defined stem cell medium, mTeSR. KMS-reprogrammed cells possess gene expression profiles akin to those of native osteo-chondroprogenitors with elevated osteogenic properties and can differentiate into osteoblasts and chondrocytes in vitro, but form bone tissue upon transplantation under the skin and in the fracture site of mouse tibia. Altogether, we provide a reprogramming strategy to enable efficient derivation of osteo-chondrogenic cells that may hold promise for cell replacement therapy not limited to cartilage but also for bone tissues.http://www.sciencedirect.com/science/article/pii/S2213671117301728chondrocytesosteoblastsosteo-chondroprogenitorsreprogrammingSOX9RUNX2c-MYCKLF4limb budlentiviruses |
| spellingShingle | Yinxiang Wang Ming-Hoi Wu May Pui Lai Cheung Mai Har Sham Haruhiko Akiyama Danny Chan Kathryn S.E. Cheah Martin Cheung Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors Stem Cell Reports chondrocytes osteoblasts osteo-chondroprogenitors reprogramming SOX9 RUNX2 c-MYC KLF4 limb bud lentiviruses |
| title | Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors |
| title_full | Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors |
| title_fullStr | Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors |
| title_full_unstemmed | Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors |
| title_short | Reprogramming of Dermal Fibroblasts into Osteo-Chondrogenic Cells with Elevated Osteogenic Potency by Defined Transcription Factors |
| title_sort | reprogramming of dermal fibroblasts into osteo chondrogenic cells with elevated osteogenic potency by defined transcription factors |
| topic | chondrocytes osteoblasts osteo-chondroprogenitors reprogramming SOX9 RUNX2 c-MYC KLF4 limb bud lentiviruses |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117301728 |
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