Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos

Malkiel A. Cohen, Katherine J. Wert, Johanna Goldmann, Styliani Markoulaki, Yosef Buganim, Dongdong Fu, Rudolf Jaenisch

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 (Wsh/Wsh), 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.

Original languageEnglish (US)
Pages (from-to)1570-1575
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number6
DOIs
StatePublished - Feb 9 2016
Externally publishedYes

Fingerprint

Neural Crest
Pigmentation
Embryonic Structures
Injections
Ectoderm
Melanocytes
Interphase
Epidermis
Hair
Mutation

Keywords

  • Chimera
  • Embryonic stem cells
  • Human neural crest cells
  • Melanocytes

ASJC Scopus subject areas

  • General

Cite this

Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos. / Cohen, Malkiel A.; Wert, Katherine J.; Goldmann, Johanna; Markoulaki, Styliani; Buganim, Yosef; Fu, Dongdong; Jaenisch, Rudolf.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 6, 09.02.2016, p. 1570-1575.

Research output: Contribution to journalArticle

Cohen, Malkiel A. ; Wert, Katherine J. ; Goldmann, Johanna ; Markoulaki, Styliani ; Buganim, Yosef ; Fu, Dongdong ; Jaenisch, Rudolf. / Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 6. pp. 1570-1575.
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