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Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons

Seifinejad, Ali, Li, Sha, Mikhail, Cyril, Vassalli, Anne, Pradervand, Sylvain, Arribat, Yoan, Pezeshgi Modarres, Hassan, Allen, Bridget, John, Rosalind M., Amati, Francesca and Tafti, Mehdi 2019. Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons. Proceedings of the National Academy of Sciences , p. 201902148. 10.1073/pnas.1902148116

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Abstract

Hypocretin (HCRT) and melanin concentrating hormone are brain neuropeptides involved in multiple functions, including sleep and metabolism. Loss of HCRT causes the sleep disorder narcolepsy. To understand how these neuropeptides are produced and contribute to diverse functions in health and disease, we purified their cells from mouse embryonic brains and established their molecular machinery. We discovered that partial removal of PEG3 (a transcription factor) in mice significantly reduces the number of HCRT and melanin concentrating hormone neurons, and its down-regulation in zebrafish completely abolishes their expression. We used our molecular data to produce these neurons in vitro from mouse fibroblasts, a technique that can be applied to cells from narcolepsy patients to generate an in vitro cell-based model.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Publisher: National Academy of Sciences
ISSN: 0027-8424
Date of First Compliant Deposit: 6 August 2019
Date of Acceptance: 7 July 2019
Last Modified: 07 Aug 2019 10:00
URI: http://orca-mwe.cf.ac.uk/id/eprint/124737

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