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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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
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 - 9 Feb 2016

Bibliographical note

Funding Information:
We thank S. Sarkar, F. Soldner, D. Maetzel, and Y. Stelzer for advice; and W. Salmon (W. M. Keck Biological Imaging Facility), Q. Gao, and R. Alagappan for experimental assistance and advice. This work was supported by Department of Defense Grant W81XWH-14-1-0057 (to R.J. and M.A.C.); by Simons Foundation Grant SFLIFE 286977; and by NIH Grants HD 045022 and R37-CA084198. K.J.W. was supported by National Cancer Institute Grant 1F32CA196965-01.

Keywords

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

Fingerprint

Dive into the research topics of 'Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos'. Together they form a unique fingerprint.

Cite this