TY - JOUR
T1 - LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency
AU - Zhang, Jin
AU - Ratanasirintrawoot, Sutheera
AU - Chandrasekaran, Sriram
AU - Wu, Zhaoting
AU - Ficarro, Scott B.
AU - Yu, Chunxiao
AU - Ross, Christian A.
AU - Cacchiarelli, Davide
AU - Xia, Qing
AU - Seligson, Marc
AU - Shinoda, Gen
AU - Xie, Wen
AU - Cahan, Patrick
AU - Wang, Longfei
AU - Ng, Shyh Chang
AU - Tintara, Supisara
AU - Trapnell, Cole
AU - Onder, Tamer
AU - Loh, Yuin Han
AU - Mikkelsen, Tarjei
AU - Sliz, Piotr
AU - Teitell, Michael A.
AU - Asara, John M.
AU - Marto, Jarrod A.
AU - Li, Hu
AU - Collins, James J.
AU - Daley, George Q.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism.
AB - The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism.
UR - http://www.scopus.com/inward/record.url?scp=85006740078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006740078&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2016.05.009
DO - 10.1016/j.stem.2016.05.009
M3 - Article
C2 - 27320042
AN - SCOPUS:85006740078
SN - 1934-5909
VL - 19
SP - 66
EP - 80
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -