title: Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos.
abstract: The neural crest (NC) represents multipotent cells that arise at the interphase between ectoderm and prospective epidermis of the neurulating embryo. The NC has major clinical relevance because it is involved in both inherited and acquired developmental abnormalities. The aim of this study was to establish an experimental platform that would allow for the integration of human NC cells (hNCCs) into the gastrulating mouse embryo. NCCs were derived from pluripotent mouse, rat, and human cells and microinjected into embryonic-day-8.5 embryos. To facilitate integration of the NCCs, we used recipient embryos that carried a c-Kit mutation (W(sh)/W(sh)), which leads to a loss of melanoblasts and thus eliminates competition from the endogenous host cells. The donor NCCs migrated along the dorsolateral migration routes in the recipient embryos. Postnatal mice derived from injected embryos displayed pigmented hair, demonstrating differentiation of the NCCs into functional melanocytes. Although the contribution of human cells to pigmentation in the host was lower than that of mouse or rat donor cells, our results indicate that hNCCs, injected in utero, can integrate into the embryo and form mature functional cells in the animal. This mouse-human chimeric platform allows for a new approach to study NC development and diseases.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Malkiel A
authors.initials: MA
authors.lastname: Cohen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Wert
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Johanna
authors.initials: J
authors.lastname: Goldmann
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Styliani
authors.initials: S
authors.lastname: Markoulaki
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Yosef
authors.initials: Y
authors.lastname: Buganim
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Dongdong
authors.initials: D
authors.lastname: Fu
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142 jaenisch@wi.mit.edu.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D001741:Black or African American; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival; D002478:Cells, Cultured; D002678:Chimera / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D054262:Gastrulation; D000066449:Human Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009432:Neural Crest / Q000166:cytology*; D016133:Polymerase Chain Reaction; D051381:Rats; D012880:Skin Pigmentation; D013045:Species Specificity; D014019:Tissue Donors
chemical_list: D004247:DNA
keywords: chimera; embryonic stem cells; human neural crest cells; melanocytes
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