期刊
DEVELOPMENT
卷 142, 期 4, 页码 633-643出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.117978
关键词
Differentiation; Hypothalamus; Narcolepsy; Neuropeptide; Pluripotent; Stem cell; Mouse; Human
资金
- Jane Coffin Childs Memorial Fund for Cancer Research
- Harvard Stem Cell Institute
- Howard Hughes Medical Institute
- National Institutes of Health [1R21NS071598, 5K99NS083713]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL109525] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM085357] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS071598, K99NS083713] Funding Source: NIH RePORTER
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.
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