Intermediate Reprogramming of Mouse Skin Fibroblasts into Stem-Like Cells by Bone Morphogenetic Protein 4.
Specific transcription factors are sufficient to reprogram fully induced pluripotent stem cells or other types of cells. These findings raise the question of whether chemical molecules or proteins can replace transcription factors to alter the defined cell fate. In this study, we treated mouse skin fibroblasts (MSFs) with bone morphogenetic protein 4 (BMP4) and examined intermediate reprogramming of MSFs into stem-like cells. Putative epidermal stem cells isolated from the ventral skin epidermis of an adult mouse were used to confirm the reprogramming activity of BMP4, which increased the proliferation of these cells. After these cells formed spheroids, they were treated with BMP4 and cultured for 5 days. Following BMP4 treatment, the characteristics of these cells changed, and they expressed Oct-4 and its target transcripts Nanog, Sox2, and alkaline phosphatase. To confirm the stem cell potency of these cells, we induced their differentiation into cardiomyocytes. Stem-like cell-derived cardiomyocytes exhibited mRNA expression of cardiac mesoderm markers such as Nk2 transcription factor-related locus 5 and connexin 40, and the cardiomyocyte marker troponin T. These differentiated cells exhibited contracting masses. These results suggest that BMP4-mediated somatic stem cell reprogramming may become an alternative approach for cell therapy.
1 Stem Cell Research Center, Jeju National University , Jeju, Korea.|2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.
Seung-Eun
SE
Lee
3 Department of Animal Science and Biotechnology, Sangji Youngseo College , Wonju, South Korea .
Sang-Jun
SJ
Uhm
1 Stem Cell Research Center, Jeju National University , Jeju, Korea.|2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.
Yeo-Jin
YJ
Son
1 Stem Cell Research Center, Jeju National University , Jeju, Korea.|2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.
Yun-Gwi
YG
Park
1 Stem Cell Research Center, Jeju National University , Jeju, Korea.|2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.|4 Mirae Cell Bio, Seoul, Korea.
Eun-Young
EY
Kim
1 Stem Cell Research Center, Jeju National University , Jeju, Korea.|2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.|4 Mirae Cell Bio, Seoul, Korea.
Se-Pill
SP
Park
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4
BMP4; MSF; putative epidermal stem cells; reprogramming; spheroid