TY  - JOUR
A1  - Chen, Geng
A1  - Schell, John Paul
A1  - Benitez, Julio Aguila
A1  - Petropoulos, Sophie
A1  - Yilmaz, Marlene
A1  - Reinius, Björn
A1  - Alekseenko, Zhanna
A1  - Shi, Leming
A1  - Hedlund, Eva
A1  - Lanner, Fredrik
A1  - Sandberg, Rickard
A1  - Deng, Qiaolin
T1  - Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
Y1  - 2016/10/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1342 
EP  - 1354 
DO  - 10.1101/gr.201954.115 
VL  - 26 
IS  - 10 
UR  - http://genome.cshlp.org/content/26/10/1342.abstract 
N2  - Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI. 
ER  -