Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts.
BACKGROUND
The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming.


RESULTS
Here, we report identification and isolation of a subpopulation of human dermal fibroblasts that express the pluripotency marker stage specific embryonic antigen 3 (SSEA3). Fibroblasts that expressed SSEA3 demonstrated an enhanced iPSC generation efficiency, while no iPSC derivation was obtained from the fibroblasts that did not express SSEA3. Transcriptional analysis revealed NANOG expression was significantly increased in the SSEA3 expressing fibroblasts, suggesting a possible mechanistic explanation for the differential reprogramming.


CONCLUSIONS
To our knowledge, this study is the first to identify a pluripotency marker in a heterogeneous population of human dermal fibroblasts, to isolate a subpopulation of cells that have a significantly increased propensity to reprogram to pluripotency and to identify a possible mechanism to explain this differential reprogramming. This discovery provides a method to significantly increase the efficiency of reprogramming, enhancing the feasibility of the potential applications based on this technology, and a tool for basic research studies to understand the underlying reprogramming mechanisms.
Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University, Palo Alto, California, United States of America.
James A
JA
Byrne
Ha Nam
HN
Nguyen
Renee A
RA
Reijo Pera
D000328:Adult; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D001706:Biopsy; D002469:Cell Separation; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007621:Karyotyping; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D012867:Skin / Q000473:pathology*; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D014158:Transcription, Genetic
D015295:Antigens, Tumor-Associated, Carbohydrate; D055746:Stage-Specific Embryonic Antigens; C052924:stage-specific embryonic antigen-3