[HTML][HTML] MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells
N Xu, T Papagiannakopoulos, G Pan, JA Thomson… - Cell, 2009 - cell.com
N Xu, T Papagiannakopoulos, G Pan, JA Thomson, KS Kosik
Cell, 2009•cell.comMicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an
important role in many developmental processes. We report here that expression of
microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but
highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2,
and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the
3′ untranslated regions of OCT4, SOX2, and KLF4. Increased miR-145 expression inhibits …
important role in many developmental processes. We report here that expression of
microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but
highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2,
and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the
3′ untranslated regions of OCT4, SOX2, and KLF4. Increased miR-145 expression inhibits …
Summary
MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an important role in many developmental processes. We report here that expression of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2, and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the 3′ untranslated regions of OCT4, SOX2, and KLF4. Increased miR-145 expression inhibits hESC self-renewal, represses expression of pluripotency genes, and induces lineage-restricted differentiation. Loss of miR-145 impairs differentiation and elevates OCT4, SOX2, and KLF4. Furthermore, we find that the miR-145 promoter is bound and repressed by OCT4 in hESCs. This work reveals a direct link between the core reprogramming factors and miR-145 and uncovers a double-negative feedback loop involving OCT4, SOX2, KLF4, and miR-145.
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