title: Human neural crest cells display molecular and phenotypic hallmarks of stem cells.
abstract: The fields of both developmental and stem cell biology explore how functionally distinct cell types arise from a self-renewing founder population. Multipotent, proliferative human neural crest cells (hNCC) develop toward the end of the first month of pregnancy. It is assumed that most differentiate after migrating throughout the organism, although in animal models neural crest stem cells reportedly persist in postnatal tissues. Molecular pathways leading over time from an invasive mesenchyme to differentiated progeny such as the dorsal root ganglion, the maxillary bone or the adrenal medulla are altered in many congenital diseases. To identify additional components of such pathways, we derived and maintained self-renewing hNCC lines from pharyngulas. We show that, unlike their animal counterparts, hNCC are able to self-renew ex vivo under feeder-free conditions. While cross species comparisons showed extensive overlap between human, mouse and avian NCC transcriptomes, some molecular cascades are only active in the human cells, correlating with phenotypic differences. Furthermore, we found that the global hNCC molecular profile is highly similar to that of pluripotent embryonic stem cells when compared with other stem cell populations or hNCC derivatives. The pluripotency markers NANOG, POU5F1 and SOX2 are also expressed by hNCC, and a small subset of transcripts can unambiguously identify hNCC among other cell types. The hNCC molecular profile is thus both unique and globally characteristic of uncommitted stem cells.
authors.affiliation: INSERM, U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Thomas
authors.forename: Marie
authors.initials: M
authors.lastname: Thomas
authors.forename: Patrick
authors.initials: P
authors.lastname: Wincker
authors.forename: Candice
authors.initials: C
authors.lastname: Babarit
authors.forename: Puting
authors.initials: P
authors.lastname: Xu
authors.forename: Marcy C
authors.initials: MC
authors.lastname: Speer
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Heather C
authors.initials: HC
authors.lastname: Etchevers
mesh_terms: D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D016000:Cluster Analysis; D018031:Connexin 43 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D033041:Embryo Research; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D015203:Reproducibility of Results; D055751:SOXC Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018031:Connexin 43; D004268:DNA-Binding Proteins; C500216:GJA1 protein, human; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein