MiR‐135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF‐β/BMP signaling
Namboori, Seema C.
Loh, Sharon Jia Hui
Stanton, Lawrence W.
Date of Issue2014
School of Biological Sciences
Several transcription factors (TFs) have been implicated in neuroectoderm (NE) development, and recently, the TF PAX6 was shown to be critical for human NE specification. However, microRNA networks regulating human NE development have been poorly documented. We hypothesized that microRNAs activated by PAX6 should promote NE development. Using a genomics approach, we identified PAX6 binding sites and active enhancers genome‐wide in an in vitro model of human NE development that was based on neural differentiation of human embryonic stem cells (hESC). PAX6 binding to active enhancers was found in the proximity of several microRNAs, including hsa‐miR‐135b. MiR‐135b was activated during NE development, and ectopic expression of miR‐135b in hESC promoted differentiation toward NE. MiR‐135b promotes neural conversion by targeting components of the TGF‐β and BMP signaling pathways, thereby inhibiting differentiation into alternate developmental lineages. Our results demonstrate a novel TF‐miRNA module that is activated during human neuroectoderm development and promotes the irreversible fate specification of human pluripotent cells toward the neural lineage.
The EMBO journal
© 2014 The Authors. This paper was published in The EMBO Journal and is made available as an electronic reprint (preprint) with permission of the Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1002/embj.201387215]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.