Identification of Embryonic Neural Plate Border Stem Cells and Their Generation by Direct Reprogramming from Adult Human Blood Cells

Cell Stem Cell. 2019 Jan 3;24(1):166-182.e13. doi: 10.1016/j.stem.2018.11.015. Epub 2018 Dec 20.


We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8.5 (E8.5) mouse neural folds. Single-cell RNA sequencing identified the anterior hindbrain as the origin of mouse NBSCs, with human iNBSCs sharing a similar regional identity. In summary, we identify embryonic NBSCs and report their generation by direct reprogramming in human, which may facilitate insights into neural development and provide a neural stem cell source for applications in regenerative medicine.

Keywords: CRISPR; NSC; direct conversion; iNSC; neural crest; neural plate border; neural progenitor; neural stem cells; regenerative medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blood Cells
  • Cell Differentiation*
  • Cells, Cultured
  • Cellular Reprogramming*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Humans
  • Male
  • Mice
  • Neural Plate / cytology*
  • Neural Plate / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Young Adult