Kisspeptin-10 treatment generated specific GnRH expression in cells differentiated from rhesus monkey derived Lyon NSCs

Neuroscience. 2017 May 4:349:318-329. doi: 10.1016/j.neuroscience.2017.03.004. Epub 2017 Mar 10.

Abstract

Embryonic stem cells (ESCs) have enormous potential as novel cell-based therapies, but their effectiveness depends on stem cell differentiation and specific signaling regulators, which remain poorly understood. In this study, a kisspeptin peptide (KP-10) was used at different dosages to determine whether rhesus macaque-derived tau GFP-Lyon ES cells underwent kisspeptin-specific neuronal differentiation. It was found that KP-10 exhibited an anti-proliferative effect on the cells and led to morphological changes and cellular differentiation consistent with neuronal stem cell (NSC) development. The cells differentiated into Gonadotrophin Releasing Hormone (GnRH) neuronal-like cell types in response to the KP-10 treatment. There has been a previously observed connection between kisspeptin signaling, GnRH neurons and their dysfunction found in congenital disorders like idiopathic hypogonadotropic hypogonadism (IHH). Although therapeutics are a still a far-off goal, the formation and development of GnRH-positive neuronal-like cells following the application of KP-10 to Lyon NSC cells opens the door for future NSC-based therapies to treat specific reproductive disorders.

Keywords: GnRH; Lyon ES; kisspeptin; neural stem cells; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Gonadotropin-Releasing Hormone / metabolism*
  • Hypogonadism / metabolism
  • Kisspeptins / pharmacology*
  • Macaca mulatta
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • KISS1 protein, human
  • Kisspeptins
  • Gonadotropin-Releasing Hormone

Supplementary concepts

  • Idiopathic Hypogonadotropic Hypogonadism