TY - JOUR
T1 - Induced multipotency in adult keratinocytes through down-regulation of Δnp63 or DGCR8
AU - Chakravarti, Deepavali
AU - Su, Xiaohua
AU - Cho, Min Soon
AU - Bui, Ngoc Hoang Bao
AU - Coarfa, Cristian
AU - Venkatanarayan, Avinashnarayan
AU - Benham, Ashley L.
AU - Flores González, Ramón E.
AU - Alana, Jennifer
AU - Xiao, Weimin
AU - Leung, Marco L.
AU - Vin, Harina
AU - Chan, Io Long
AU - Aquino, Arianexys
AU - Müller, Nicole
AU - Wang, Hongran
AU - Cooney, Austin J.
AU - Parker-Thornburg, Jan
AU - Tsai, Kenneth Y.
AU - Gunaratne, Preethi H.
AU - Flores, Elsa R.
PY - 2014/2/4
Y1 - 2014/2/4
N2 - The roles of microRNAs (miRNAs) and the miRNA processing machinery in the regulation of stem cell biology are not well understood. Here, we show that the p53 family member and p63 isoform, ΔNp63, is a transcriptional activator of a cofactor critical for miRNA processing (DGCR8). This regulation gives rise to a unique miRNA signature resulting in reprogramming cells to multipotency. Strikingly, ΔNp63-/- epidermal cells display profound defects in terminal differentiation and express a subset of markers and miRNAs present in embryonic stem cells and fibroblasts induced to pluripotency using Yamanaka factors. Moreover, ΔNp63-/- epidermal cells transduced with an inducible DGCR8 plasmid can differentiate into multiple cell fates in vitro and in vivo. We found that human primary keratinocytes depleted of ΔNp63 or DGCR8 can be reprogrammed in 6 d and express a unique miRNA and gene expression signature that is similar but not identical to human induced pluripotent stem cells. Our data reveal a role for ΔNp63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells.
AB - The roles of microRNAs (miRNAs) and the miRNA processing machinery in the regulation of stem cell biology are not well understood. Here, we show that the p53 family member and p63 isoform, ΔNp63, is a transcriptional activator of a cofactor critical for miRNA processing (DGCR8). This regulation gives rise to a unique miRNA signature resulting in reprogramming cells to multipotency. Strikingly, ΔNp63-/- epidermal cells display profound defects in terminal differentiation and express a subset of markers and miRNAs present in embryonic stem cells and fibroblasts induced to pluripotency using Yamanaka factors. Moreover, ΔNp63-/- epidermal cells transduced with an inducible DGCR8 plasmid can differentiate into multiple cell fates in vitro and in vivo. We found that human primary keratinocytes depleted of ΔNp63 or DGCR8 can be reprogrammed in 6 d and express a unique miRNA and gene expression signature that is similar but not identical to human induced pluripotent stem cells. Our data reveal a role for ΔNp63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells.
UR - http://www.scopus.com/inward/record.url?scp=84893455185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893455185&partnerID=8YFLogxK
U2 - 10.1073/pnas.1319743111
DO - 10.1073/pnas.1319743111
M3 - Article
C2 - 24449888
AN - SCOPUS:84893455185
SN - 0027-8424
VL - 111
SP - E572-E581
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -