| RRC ID |
58801
|
| 著者 |
Umehara Y, Toyama S, Tominaga M, Matsuda H, Takahashi N, Kamata Y, Niyonsaba F, Ogawa H, Takamori K.
|
| タイトル |
Robust induction of neural crest cells to derive peripheral sensory neurons from human induced pluripotent stem cells.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Because intractable itch reduces quality of life, understanding the fundamental mechanisms of itch is required to develop antipruritic treatments. Itch is mediated by peripheral sensory neurons, which originate from the neural crest (NC) during development. Itch-associated signaling molecules have been detected in genetically engineered animals and in cultures of peripheral neurons from dorsal root ganglia (DRG). Ethical difficulties collecting peripheral neurons from human DRG have limited analysis of itch in humans. This study describes a method of differentiating peripheral neurons from human induced pluripotent stem cells (hiPSCs) for physiological study of itch. This method resulted in the robust induction of p75 and HNK1 double-positive NC cells from hiPSCs. The expression of NC markers TFAP2A, SOX10 and SNAI1 increased during NC induction. The induction efficiency was nearly 90%, and human peripheral neurons expressing peripherin were efficiently differentiated from hiPSC-derived NC cells. Moreover, induced peripheral neurons expressed the sensory neuronal marker BRN3A and the itch-related receptors HRH1, MRGPRX1, IL31R and IL-4R. Calcium imaging analyses indicated that these peripheral neurons included sensory neurons responsive to itch-related stimuli such as histamine, BAM8-22, IL-31 and IL-4. These findings may enable detailed analyses of human DRG neurons and may result in new therapies for intractable itch.
|
| 巻・号 |
10(1)
|
| ページ |
4360
|
| 公開日 |
2020-3-9
|
| DOI |
10.1038/s41598-020-60036-z
|
| PII |
10.1038/s41598-020-60036-z
|
| PMID |
32152328
|
| PMC |
PMC7063040
|
| MeSH |
Apoptosis
Biomarkers
Cell Differentiation* / genetics
Cells, Cultured
Fluorescent Antibody Technique
Humans
Immunophenotyping
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / drug effects
Induced Pluripotent Stem Cells / metabolism*
Neural Crest / cytology*
Neurogenesis
Sensory Receptor Cells / cytology*
Sensory Receptor Cells / metabolism*
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063) |
