‘Pacemaker’ channels in hair stem cells offer clues to tissue regeneration, say Stanford researchers
The growth of hair on your head (and elsewhere on your body, for that matter) is a tightly regulated and fascinating biological activity. Researchers are particularly interested in understanding how the stem cells in the hair follicles, which are called bulge cells, know how and when to cycle in and out of dormancy. Learning more about this process, they believe, may provide the insight necessary to harness the regenerative capacity of many types of stem cells for tissue repair and renewal.
This week, Stanford dermatologist Anthony Oro, MD, PhD, and colleagues published a study (subscription required) in Genes and Development of a mouse model they developed of a human condition called Timothy syndrome. Patients with Timothy syndrome are born bald and often take months or years to develop any hair. They also suffer from cardiac abnormalities and physical malformations and usually die at a tragically young age. But they have a very interesting genetic mutation. As Oro explained to me:
Stem cells exhibit the ability to cyclically regenerate organs, but what controls the timing of activation remains a puzzle. Timothy syndrome (TS) patients carry mutations in a calcium channel called Cav1.2 that controls the timing of the heartbeat. TS patients exhibit both cardiac arrhythmia and a significant delay in the activation of the hair cycle.
Oro and his colleagues, including Stanford postdoctoral scholar and the study’s first author Gozde Yucel, PhD, were puzzled as to why bulge cells, which (they showed in their study) don’t respond to or rely on the electrical and molecular pulses that drive cardiac cells, would even have a calcium channel. They used mouse genetics and pharmacology to investigate the abnormality in hair stem cell timing in the animals with a similar mutation. They found that, in the mice, the channel functions to control the levels of stem cell regulators responsible for tissue regeneration. According to Oro:
These surprising results demonstrate a wider function for pacemaker channels in tissue stem cells, and suggest the existence of channel ligands that have therapeutic applications in regenerative medicine.