Human skin cells converted into pain sensing neurons

Scientists have converted human skin cells into specialised neurons that detect pain, itch, touch and other bodily sensations.
These neurons are also affected by spinal cord injury and are involved in Friedreich's ataxia, a devastating and currently incurable neurodegenerative disease that largely strikes children, researchers said.
The advance allows this broad class of human neurons and their sensory mechanisms to be studied relatively easily in the laboratory, said the team led by scientists from The Scripps Research Institute (TSRI).
"Following on the work of TSRI Professor Ardem Patapoutian, who has identified many of the genes that endow these neurons with selective responses to temperature, pain and pressure, we have found a way to produce induced sensory neurons from humans where these genes can be expressed in their 'normal' cellular environment," said associate Professor Kristin K Baldwin, an investigator in TSRI's Dorris Neuroscience Center.

"This method is rapid, robust and scalable. Therefore we hope that these induced sensory neurons will allow our group and others to identify new compounds that block pain and itch and to better understand and treat neurodegenerative disease and spinal cord injury," Baldwin said.
The neurons that can be made with the new technique normally reside in clusters called dorsal root ganglia (DRG) along the outer spine.

For the new study, the team used a cell-reprogramming technique (similar to those used to reprogramme skin cells into stem cells) to generate human DRG-type sensory neurons from ordinary skin cells called fibroblasts.

The scientists examined previous experiments and identified several transcription factors - managerial proteins that switch on the activity of large sets of genes - that seemed crucial to the ability of immature neurons to develop into adult sensory neurons.
They found that the combination of the transcription factors Brn3a plus Ngn1, or Brn3a plus Ngn2, reprogrammed a significant percentage of the embryonic mouse fibroblasts into what looked - and acted - like mature DRG-type sensory neurons.
"We added compounds including capsaicin, which activates pain receptors on DRG neurons, and menthol, which activates cold receptors, and saw subsets of our induced neurons light up with activity just as real DRG neurons would," said co-lead author of the study Kevin T Eade.

Using the same recipes of transcription factors, the team was able to convert adult human fibroblasts, which are harder to reprogramme, into DRG neurons.
The conversion rate was lower, but the induced neurons seemed just as much like their natural counterparts as those produced from embryonic mouse fibroblasts.
The study is published in the journal Nature Neuroscience.