[초청강연] The functions and epigenetic regulations of hair follicle stem cells

The functions and epigenetic regulations of hair follicle stem cells

Hanseul Yang

Department of Biological Science, KAIST, Daejeon, Korea

Tissue regeneration relies on resident stem cells, whose activity and lineage choices are
influenced by microenvironment. Once activated, stem cells typically give rise to short-lived
progenitors, which then progress to differentiate into their lineages. Exploiting the synchronized
cyclical bouts of tissue regeneration in hair follicles, we investigated when and how stem cell
lineage choices take place. Using temporal single-cell RNA-seq and in vivo lineage tracing, we
unearthed unexpected heterogeneity among stem cells and their progeny and found that the
ability of stem cells to make lineage choices (plasticity) becomes restricted in a sequentially and
spatially choreographed program. We traced the roots of lineage restriction to micro-niches
located along epithelial-mesenchymal borders, each of which receive slightly different signaling
inputs. Instructed by micro-niches signals, hair follicle stem cells reorganize their super-enhancer
network to achieve lineage switches. Dissecting the dynamic epigenetic remodeling, we uncover
transcription factors NFIB and NFIX as guardians of SC maintenance. Without NFIs, hair
follicle stem cells cannot survive, generating skin bearing striking resemblance to irreversible
human alopecia, which also displays reduced NFIs. Through single cell transcriptomics, ATAC-
seq and ChIP-seq profiling, we uncover a key role for NFIB/NFIX in governing super-enhancer
maintenance of the key hair follicle stem cell specific transcription factor genes. When
NFIB/NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers
driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically.
Together, our findings expose NFIB/NFIX as crucial rheostats of tissue homeostasis, functioning
to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers
irreversible tissue degeneration.