A pinboard by
Hanseul Yang

Graduate Student, The Rockefeller University


Adult tissue regeneration and stem cells

Adult tissue stem cells (SCs) reside in niches, which, through intercellular contacts and signaling, influence SC behavior. During tissue regeneration, adult SCs become activated and typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Despite the well-defined characteristics and lineage potential of stem cells, it remains unclear where and how fate decision and lineage-restricted maturation steps are taking place. The answers are at the crux of our understanding of how adult tissue regeneration works, how stem cells become progressively restricted in their fate choices and what happens in human disease states when lineage choices go awry.

To begin to address these important problems, I took advantage of the mouse hair follicle (HF), where its stem cells, niche and master transcriptional regulators are well characterized, spatial parent-daughter context is well-defined, and its seven concentric lineages are well-organized. I employed temporal single-cell RNA-sequencing on purified populations of in vivo stem cells, their progeny, and micro-environment counterparts as they progress through their journey from quiescence to progeny that actively regenerate tissue. Through a high-resolution view of lineage diversification combined with lineage-tracing, I have gained major new insights into stem cell specification.

Using single-cell RNA-seq, I unearthed unexpected heterogeneity among SCs and TACs of hair follicles. I traced the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage tracing, temporal single-cell analyses, and chromatin landscaping, I showed that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged unilineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: some progenitors specify lineages immediately, whereas others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment.