TY - JOUR
T1 - Sphere formation permits oct4 reprogramming of ciliary body epithelial cells into induced pluripotent stem cells
AU - Ni, Aiguo
AU - Wu, Ming Jing
AU - Chavala, Sai H.
N1 - Publisher Copyright:
© Copyright 2014, Mary Ann Liebert, Inc. 2014.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by defined sets of transcription factors. We previously described reprogramming of monolayer-cultured adult mouse ciliary body epithelial (CE) cells by Oct4 and Klf4, but not with Oct4 alone. In this study, we report that Oct4 alone is sufficient to reprogram CE cells to iPS cells through sphere formation. Furthermore, we demonstrate that sphere formation induces a partial reprogramming state characterized by expression of retinal progenitor markers, upregulation of reprogramming transcription factors, such as Sall4 and Nanog, demethylation in the promoter regions of pluripotency associated genes, and mesenchymal to epithelial transition. The Oct4-iPS cells maintained normal karyotypes, expressed markers for pluripotent stem cells, and were capable of differentiating into derivatives of all three embryonic germ layers in vivo and in vitro. These findings suggest that sphere formation may render somatic cells more susceptible to reprogramming.
AB - Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by defined sets of transcription factors. We previously described reprogramming of monolayer-cultured adult mouse ciliary body epithelial (CE) cells by Oct4 and Klf4, but not with Oct4 alone. In this study, we report that Oct4 alone is sufficient to reprogram CE cells to iPS cells through sphere formation. Furthermore, we demonstrate that sphere formation induces a partial reprogramming state characterized by expression of retinal progenitor markers, upregulation of reprogramming transcription factors, such as Sall4 and Nanog, demethylation in the promoter regions of pluripotency associated genes, and mesenchymal to epithelial transition. The Oct4-iPS cells maintained normal karyotypes, expressed markers for pluripotent stem cells, and were capable of differentiating into derivatives of all three embryonic germ layers in vivo and in vitro. These findings suggest that sphere formation may render somatic cells more susceptible to reprogramming.
UR - http://www.scopus.com/inward/record.url?scp=84916883538&partnerID=8YFLogxK
U2 - 10.1089/scd.2014.0064
DO - 10.1089/scd.2014.0064
M3 - Article
C2 - 25027059
AN - SCOPUS:84916883538
SN - 1547-3287
VL - 23
SP - 3065
EP - 3071
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 24
ER -