Redefining the structure of the hair follicle by 3D clonal analysis

Abstract

SUMMARYThe hair follicle (HF) is a multi-tissue mini-organ that self-renews periodically. However, the cellular organisation of this much-studied model is not fully understood. The structures of the outer layer and of the bulb, which ensures HF growth, have not been completely established. To clarify these points, we have conducted in vivo clonal analyses with 3D imaging in mice. The upper two-thirds of the HF outer layer consists of two clonally unrelated groups of cells that exhibit different modes of growth. They correspond to the basal outer root sheath (ORS) and the companion layer (Cp). The basal ORS has an unusual anisotropic mode of growth from a suprabulbar zone, which we named the privileged proliferation zone. The Cp has a stem/transient-amplifying mode of growth and is shown to be an HF internal structure. Furthermore, we describe an additional element, the bulb outer layer, which is contiguous and shares markers (e.g. Lgr5) with the basal ORS but is formed by a separate lineage that belongs neither to the ORS nor Cp lineage. It represents a novel element with proximal cells that are contiguous with the germinative layer in the bulb. In reference to its shape and position we named it the lower proximal cup (LPC). These clonal hierarchies reveal a novel model of HF organisation and growth based on two major entities: the basal ORS and the LPC plus the seven internal layers.

Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy

“…HFs suffering from a more dystrophic change regenerate from the surviving ORS cells. Although our lineage studies are not able to directly differentiate between K5 + basal bulb cells and K5 + basal ORS cells, the two cell populations are known to be distinct in origin and function during anagen (14). K5 + hair bulb cells broadly apoptose after 5.5Gy, indicating that radioresistant K5 + ORS cells are the most likely origin for the epithelial strand.…”

“…In hair bulbs, germinative and basal bulb cells are thought to represent two distinct lineages within the TAC population (14). Proliferative germinative cells fuel hair shaft elongation (14,45) while basal hair bulb cells (also referred to as lower proximal cup cells) are speculated to maintain the shape of hair bulbs and not to contribute to the inner HF structures (14).…”

“…Proliferative germinative cells fuel hair shaft elongation (14,45) while basal hair bulb cells (also referred to as lower proximal cup cells) are speculated to maintain the shape of hair bulbs and not to contribute to the inner HF structures (14). We show that K5 + basal cells serve as SCs for rapid repair of the HF bulb, and that their concealed plasticity is quickly unveiled upon injury.…”

BMP Signaling and Its pSMAD1/5 Target Genes Differentially Regulate Hair Follicle Stem Cell Lineages

“…The cuticle and Huxley IRS layers express transcription factor GATA3 and structural protein trichohyalin (AE15+), while the companion layer (CP) between IRS and ORS is marked by keratin 6 (K6), also found in the medulla. Each of their progenitor pools have been lineage traced to the matrix TACs in a spatial distribution that recapitulates this differentiated layering (Fuchs, 2007; Sequeira and Nicolas, 2012). …”

Preparation and Delivery of 4-Hydroxy-Tamoxifen for Clonal and Polyclonal Labeling of Cells of the Surface Ectoderm, Skin, and Hair Follicle

“…The binding of 4-OHT induces its activation and the modification of the conditional reporter gene by the recombinase. As a result, the labeled cells and their descendants carry the modified reporter gene and form clones that can be identified by X-gal staining (11) or immunofluorescence mT/mG (12).…”