Skip to main content
eScholarship
Open Access Publications from the University of California

Rapid neurogenesis through transcriptional activation in human stem cells

  • Author(s): Busskamp, V
  • Lewis, NE
  • Guye, P
  • Ng, AH
  • Shipman, SL
  • Byrne, SM
  • Sanjana, NE
  • Murn, J
  • Li, Y
  • Li, S
  • Stadler, M
  • Weiss, R
  • Church, GM
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299601/
No data is associated with this publication.
Abstract

© 2014 The Authors. Published under the terms of the CC BY 4.0 license. Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems-level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item