Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

Florian T. Merkle, Asif Maroof, Takafumi Wataya, Yoshiki Sasai, Lorenz Studer, Kevin Eggan, Alexander F. Schier

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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, agoutirelated 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.

Original languageEnglish (US)
Pages (from-to)633-643
Number of pages11
JournalDevelopment (Cambridge)
Volume142
Issue number4
DOIs
StatePublished - Feb 15 2015
Externally publishedYes

Keywords

  • Differentiation
  • Human
  • Hypothalamus
  • Mouse
  • Narcolepsy
  • Neuropeptide
  • Pluripotent
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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