Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

Development. 2015 Feb 15;142(4):633-43. doi: 10.1242/dev.117978.

Abstract

Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases.

Keywords: Differentiation; Human; Hypothalamus; Mouse; Narcolepsy; Neuropeptide; Pluripotent; Stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / metabolism
  • Arginine Vasopressin / metabolism
  • Humans
  • Hypothalamic Hormones / metabolism
  • Hypothalamus / cytology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Melanins / metabolism
  • Neurons / cytology*
  • Neuropeptides / metabolism
  • Orexins
  • Oxytocin / metabolism
  • Pituitary Hormones / metabolism
  • Pluripotent Stem Cells / cytology*
  • Pro-Opiomelanocortin / metabolism
  • Thyrotropin-Releasing Hormone / metabolism

Substances

  • Agouti-Related Protein
  • Hypothalamic Hormones
  • Intracellular Signaling Peptides and Proteins
  • Melanins
  • Neuropeptides
  • Orexins
  • Pituitary Hormones
  • Arginine Vasopressin
  • Oxytocin
  • Thyrotropin-Releasing Hormone
  • Pro-Opiomelanocortin
  • melanin-concentrating hormone