Biochemistry Through the Language Barrier was the topic of an earlier blog post.
Here I present: Human Cell Atlas (HCA): The Integument (Skin).
In the Human Cell Atlas (HCA), the integumentary system refers to the skin and its appendages—hair follicles, sweat glands, sebaceous glands, nails, and associated immune, vascular, and sensory structures.
The goal of HCA is to map every cell type in the human body. For skin, this means cataloguing all the diverse cells that build barriers, sense the world, and protect the body from harm.
Major Cell Types of the Skin in HCA
1. Keratinocytes (K) – Barrier Builders
Make up the epidermis.
Produce keratin → strong protective barrier.
Organized in layers: basal, spinous, granular, cornified.
Include stem cells in the basal layer.
2. Melanocytes (Pigment; P)
Produce melanin.
Protect DNA from ultraviolet (UV) radiation.
Reside in the basal epidermis and hair follicles.
3. Immune Cells (I)
Skin is an immune organ.
Langerhans cells (special dendritic cells in the epidermis).
Dermal dendritic cells.
Macrophages.
T-cells (including resident memory T-cells).
Mast cells.
4. Sensory Cells (S)
Merkel cells (touch).
Free nerve endings (pain, temperature).
Associated Schwann cells.
5. Fibroblasts & Matrix Cells (M)
Located in the dermis.
Produce collagen, elastin, extracellular matrix.
Different fibroblast states identified by scRNA-seq (e.g., papillary vs reticular).
6. Appendage Cells
Hair Follicle
Germinal (G) stem cells
Matrix (M) cells
Inner/outer root sheath
Melanocyte subtypes
Dermal papilla cells
Sweat glands (Eccrine/Apocrine)
Duct cells
Secretory cells (exocrine; X)
Sebaceous glands
Sebocytes (lipid-producing)
7. Vascular Cells
Endothelial cells (B: barrier, plus vascular-specialized transcriptional states).
Pericytes and smooth muscle cells (C: contractile).
Why Skin Is Important in HCA.
It is the largest organ and highly accessible for sampling.
Shows enormous spatial variation (scalp vs palm vs mucosa).
Contains: stem cell niches, immune–epithelial interactions, and aging signatures.
Plays roles in wound healing, inflammation, infection, and cancer.
How HCA Studies Skin.
Techniques commonly used:
scRNA-seq: profiles epidermis, appendages, immune cells, fibroblasts.
snRNA-seq: for deeper or fibrous dermal tissue.
Spatial transcriptomics (Visium, MERFISH): to map cells in place.
ATAC-seq: identifies regulatory elements’ driving cell identity.
