Single-cell RNA sequencing of human epidermis identifies Lunatic fringe as a novel regulator of the stem cell compartment.

Single-cell RNA sequencing (scRNA-seq) of human skin provides a tool for validating observations from in vitro experimental models. By analyzing a published dataset of healthy adult epidermis, we confirm that the basal epidermal layer is heterogeneous, and three subpopulations of non-dividing cells can be distinguished. We show that Delta-like ligand 1 (DLL1) is expressed in a subset of basal cells previously identified as stem cells in cultured human keratinocytes and map the distribution of other Notch ligands and receptors to specific epidermal cell compartments.

A reductionist approach to determine the effect of cell-cell contact on human epidermal stem cell differentiation.

The balance between stem cell renewal and differentiation is determined by the interplay between intrinsic cellular controls and extrinsic factors presented by the microenvironment, or 'niche'. Previous studies on cultured human epidermis have utilised suspension culture and restricted cell spreading to investigate regulation of differentiation in single keratinocytes. However, keratinocytes are typically adherent to neighbouring cells in vivo.

Dynamic regulation of human epidermal differentiation by adhesive and mechanical forces.

The interfollicular epidermis is the multilayered epithelium that forms the outer layer of the skin. It is maintained by stem cells that are attached to a basement membrane, which lies on top of the underlying connective tissue, the dermis. Cells undergo terminal differentiation as they detach from the basement membrane and move toward the outer epidermal surface.

Patterning of human epidermal stem cells on undulating elastomer substrates reflects differences in cell stiffness.

In human skin the junction between epidermis and dermis undulates, the width and depth of the undulations varying with age and disease. When primary human epidermal keratinocytes are seeded on collagen-coated polydimethylsiloxane (PDMS) elastomer substrates that mimic the epidermal-dermal interface, the stem cells become patterned by 24 h, resembling their organisation in living skin. We found that cell density and nuclear height were higher at the base than the tips of the PDMS features.

The "nuclear physics" behind epigenetic control of cell fate.

It is well understood that replicative and transcriptional responses in the nucleus occur under the influence of specific extracellular biochemical signals (e.g. growth factors and cytokines).

Micro-scaled topographies direct differentiation of human epidermal stem cells.

Human epidermal stem cells initiate terminal differentiation when spreading is restricted on ECM-coated micropatterned islands, soft hydrogels or hydrogel-nanoparticle composites with high nanoparticle spacing. The effect of substrate topography, however, is incompletely understood. To explore this, primary human keratinocytes enriched for stem cells were seeded on a topographical library with over 2000 different topographies in the micrometre range.

Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis.

Osteoclasts (OCs) originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM) by flow cytometry and assessed their differentiation potential in vitro. Within the CD11b(-)CD34(+)c-KIT(+) BM cell population, OC-differentiation potential was restricted to FLT3(+) cells and enriched in an IL3 receptor (R)α(high) subset that constituted less than 0.

Liquid biopsies in patients with diffuse glioma.

Diffuse gliomas are the most common malignant primary tumors of the central nervous system. Like other neoplasms, these gliomas release molecular information into the circulation. Tumor-derived biomarkers include proteins, nucleic acids, and tumor-derived extracellular vesicles that accumulate in plasma, serum, blood platelets, urine and/or cerebrospinal fluid.