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Let-7 miRNAs can act through NOTCH to regulate human gliogenesis

  • Author(s): Patterson, M
  • Gaeta, X
  • Loo, K
  • Edwards, M
  • Smale, S
  • Cinkornpumin, J
  • Xie, Y
  • Listgarten, J
  • Azghadi, S
  • Douglass, SM
  • Pellegrini, M
  • Lowry, WE
  • et al.
Abstract

© 2014 The Authors. It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let- 7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.

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