MicroRNAs (miRNAs) play critical roles in modulating stem cell pluripotency and their differentiation, but the general fundamental mechanism remains largely unknown. This study systematically reveals the general roles of miRNAs in mouse pluripotent stem cells by analyzing a physical interaction network constructed from miRNA and protein binding data generated by next-generation sequencing . Generally, miRNAs vary their suppressor roles in different cellular developmental stages, a pluripotent stateor a differential state . During pluripotency , miRNAs primarily repress developmental processes while they inhibit metabolism in the differential state. Interestingly, in the pluripotent state, miRNAs do not directly regulate the pluripotent core activities but mediate extrinsic signal pathways associated with the pluripotency; however in the differential state, miRNAs directly repress the pluripotency. Mechanically , DNA methylation in enhancer regions mediates these miRNA activations. Together, under mediation by DNA methylation, miRNAs directly repress development but only modulate the pluripotent signal pathways in the pluripotent state; while in the developmental state miRNAs directly suppress both metabolism and pluripotency .
MicroRNAs (miRNAs) critically modulate stem cell pluripotency and their differentiation, but the precise mechanistic mechanism remains largely unknown. This study systematically reveals the functional and mechanistic roles of miRNAs in mouse pluripotent stem cells by analyzing the genome-wide physical interactions between all activated miRNAs and their targets . Generally, miRNAs vary their physical targets and functions with the switch of pluripotency to differentiation state . During pluripotency miRNAs primarily and mechanistically target and repress developmental processes , but surprisingly miRNAs do not directly target the pluripotent core factors but only mediate extrinsic signal pathways associated with pluripotency. During differentiation miRNAs mechanistically inhibit metabolism and directly repress the pluripotency. Interestingly , DNA methylation in enhancer regions mediates these miRNA activations. Together, under mediation by DNA methylation, miRNAs directly repress development and mechanistically modulate the pluripotent signal pathways to help stem cells maintain pluripotency; yet miRNAs directly repress both pluripotency and metabolism to facilitate cell differentiation .
R
play critical roles in modulating
critically modulate
R
general fundamental
precise mechanistic
R
general
functional and mechanistic
R
a physical interaction network constructed from miRNA and protein binding data generated by next-generation sequencing
the genome-wide physical interactions between all activated miRNAs and their targets
R
suppressor roles in different cellular developmental stages, a pluripotent stateor a differential state
physical targets and functions with the switch of pluripotency to differentiation state
R
, miRNAs primarily
miRNAs primarily and mechanistically target and
R
while they inhibit metabolism in the differential state. Interestingly, in the pluripotent state,
, but surprisingly
R
regulate
target
R
activities but
factors but only
R
the pluripotency; however in the differential state, miRNAs
pluripotency. During differentiation miRNAs mechanistically inhibit metabolism and
R
Mechanically
Interestingly
R
but only
and mechanistically
R
in the pluripotent state; while in the developmental state miRNAs directly suppress both metabolism and pluripotency
to help stem cells maintain pluripotency; yet miRNAs directly repress both pluripotency and metabolism to facilitate cell differentiation