Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Regenerative Medicine

Background:

• Neural crest (NC) cells originate from the neural plate border in vertebrate embryos.
• NC cells undergo an epithelial-to-mesenchymal transition for migration and differentiation into various cell types.

Purpose of the Study:

• To investigate if postnatal human epidermal keratinocytes (KC) can be reprogrammed into NC cells.
• To characterize the NC-like cells derived from KC and their differentiation potential.

Main Methods:

• Reprogramming of human keratin-14+ KC using fibroblast growth factor 2 and insulin-like growth factor 1.
• Genome-wide transcriptome analysis to compare KC-derived NC cells with embryonic stem cell-derived NC cells.
• In vitro and in vivo differentiation assays to assess the potential of KC-derived NC cells.

Main Results:

• Postnatal human KC successfully reprogrammed to a NC fate.
• Transcriptome analysis confirmed similarity between KC-derived and embryonic stem cell-derived NC cells.
• KC-derived NC cells differentiated into peripheral neurons, melanocytes, Schwann cells, and mesenchymal cells (osteocytes, chondrocytes, adipocytes, smooth muscle cells).

Conclusions:

• Human keratinocytes can be reprogrammed into neural crest cells, even from single-cell clones.
• This finding has significant implications for stem cell biology and regenerative medicine applications.