title: Notch signaling regulates the differentiation of neural crest from human pluripotent stem cells.
abstract: Neural crest cells are specified at the border between the neural plate and the epiderm. They are capable of differentiating into various somatic cell types, including craniofacial and peripheral nerve tissues. Notch signaling plays important roles during neurogenesis; however, its function during human neural crest development is poorly understood. Here, we generated self-renewing premigratory neural-crest-like cells (pNCCs) from human pluripotent stem cells (hPSCs) and investigated the roles of Notch signaling during neural crest differentiation. pNCCs expressed various neural-crest-specifier genes, including SLUG (also known as SNAI2), SOX10 and TWIST1, and were able to differentiate into most neural crest derivatives. Blocking Notch signaling during the pNCC differentiation suppressed the expression of neural-crest-specifier genes. By contrast, ectopic expression of activated Notch1 intracellular domain (NICD1) augmented the expression of neural-crest-specifier genes, and NICD1 was found to bind to their promoter regions. Notch activity was also required for the maintenance of the premigratory neural crest state, and the suppression of Notch signaling led to the generation of neural-crest-derived neurons. Taken together, we provide a protocol for the generation of pNCCs and show that Notch signaling regulates the formation, migration and differentiation of neural crest from hPSCs.
authors.affiliation: School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Parinya
authors.initials: P
authors.lastname: Noisa
authors.forename: Carina
authors.initials: C
authors.lastname: Lund
authors.forename: Kartiek
authors.initials: K
authors.lastname: Kanduri
authors.forename: Riikka
authors.initials: R
authors.lastname: Lund
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.forename: Karolina
authors.initials: K
authors.lastname: Lundin
authors.forename: Hataiwan
authors.initials: H
authors.lastname: Chokechuwattanalert
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.forename: Timo
authors.initials: T
authors.lastname: Tuuri
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D051880:Receptors, Notch; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1
keywords: Human embryonic stem cells; Human induced pluripotent stem cells; Neural crest; Notch signaling