Collective Mechanism of Hair Regrowth during Alopecia Areata Resolution
This project aims to evaluate evidence that progression from telogen to anagen growth follows a wave pattern by repeated evaluation with optical coherence tomography imaging; and to perform single cell sequencing to identify factors that predict progression to anagen.
In alopecia areata (AA), thousands of actively growing (anagen) scalp hair follicles transition into a dormant (telogen) state. When AA resolves, either spontaneously or in response to JAK inhibitor treatment, the newly formed anagen follicles re-emerge rapidly in what grossly appear to be spreading waves. This growth pattern is commonly seen in rodents, where spreading waves are the outcome of a collective behavior, when anagen follicles signal to activate neighboring telogen follicles to also enter anagen in a chain-like reaction. This mechanism leads to a highly efficient anagen activation across large regions of skin. Inspired by our preliminary data on hair regrowth patterns in JAK inhibitor-treated AA patients, in this pilot application we propose to definitively establish the existence of a wave-like mechanism for anagen activation in human scalp, using optical coherence tomography imaging coupled with histological analysis of re-growing wave-front in AA. We will also collect single-cell RNA-sequencing data from wave-front hair-bearing skin and compare its cellular composition and key molecular changes to those of adjacent alopecic areas. High throughput single-cell data will be used to develop hypotheses on cellular and signaling changes that accompany collective AA hair regrowth, previously undescribed in human hair. We will be able to identify hair regeneration-associated changes in intra- and peri-follicular cell types, including immune cells, and key inhibitory and activating signaling factor changes. The hypothesis proposed herein is novel for the AA field, and its results will significantly advance the understanding of AA resolution mechanisms and open new lines of AA research.
If successful, this study could provide important mechanistic insights into hair biology, identify novel molecular targets for anagen activation, and lead to the development of new growth factor-based strategies for enhanced hair regeneration in patients with alopecia areata.