Beauty Note | Formation of New Skin Cells

Formation of new skin cells involves constant shedding of old/dead skin cells and subsequent replacement with younger skin cells. Every formation, sloughing and replacement of the skin cell are categorized as a cycle of skin cell production. Before we get through the topic deeply, let's get started with the structure of our skin. Basically, our skin structure consists of three important layers which are epidermis, dermis and hypodermis. Among of these three layers, epidermis is where the renewal of skin cells occur.

Structure of skin.

Epidermis is the outermost layer of human skin. It forms the waterproof, protective wrap over the body surface and is made up of a stratified squamous epithelium with an underlying basal lamina. It is composed of four main types of cells namely keratinocytes, melanocytes, Langerhans cells and Merkel cells. Keratinocytes is the cells that make proteins called keratin, which is the predominant type of cells in the epidermis.

Before we go to what exactly happen in epidermis during the skin renewal processes, let's first see how many sublayers are existed in the epidermis layer. Basically, epidermis layer is made of 5 sublayers which are (from deepest to the most superficial layer) :

1. Stratum Germinativum
2. Stratum Spinosum
3. Stratum Granulosum
4. Stratum Lucidum
5. Stratum Corneum

Structure of epidermis layer.

📌 1. Stratum Germinativum

Stratum Germinativum is known as layer of stem cells. It is where the new skin cells, more specifically, keratinocytes are originated, which is from stem cells. Stem cells are undifferentiated cells that undergo cell division or replication for many times forming more cells called daughter cells. These daughter can either become new stem cells (self-renewal) or become specialized cells (differentiation) with more specific functions such as blood cells, bone cells, brain cells - in this case, keratinocytes, to provide a structure and rigidity as well as barrier protection to a skin by producing keratin.

Stem cell division.

Formation of keratinocyte from stem cell.

In this sublayer, stem cells give rise to short-lived keratinocyte progenitors. After dividing for many times and almost reaching the next layer, keratinocyte progenitors start to form suprabasal keratinocytes.

Basal and suprabasal layers of epidermis.

There are two other cells found in this layer namely Merkel cell and melanocytes. Merkel cells act as receptors and it are responsible in stimulating sensory nerves that the brain perceives as touch. Melanocytes are responsible for the production of melanosomes, in which the melanin pigment is synthesized and deposited to give skin its colour and tone. Melanosomes are transferred from melanocytes to neighboring keratinocytes in order to form perinuclear melanin caps.

Structure of epidermis.

Transferal of melanosome into keratinocytes.

Cytoplasm of keratonocytes contains a lot of scattered tonofilaments which then aggregate forming bundles of filaments called tonofibrils. These tonofibrils are responsible in the formation of desmosomes/hemidesmosomes that attach the cells to one another and to dermis layer/basement membrane.

Cytoplasmic organelles of keratinocyte.

Hemidesmosome and desmosome.

📌 2. Stratum Spinosum

In Stratum Spinosum, keratonocytes differentiate gradually via mitosis to proliferate and amplify keratinocytes population as they getting composing the next sublayers. As new keratinocyte progenitors, as well as suprabasal keratinocytes are gradually formed, the existing keratinocytes are pushed superficially migrating away from this layer forming other strata (stratum) while differentiating, changing their structure and function.

On the other words, the existing keratinocytes travel up within the epidermis layer while flattening out, until it reach the uppermost layer of the skin which is Stratum Corneum. As newer keratinocytes continually travelling up, oldest cell die and rise to the skin surface and slough off.

Langerhans cells or known as special immune cells,  are found in this sublayer. These cells are able to engulf foreign substances and damaged cells that occur within epidermis layer.

While keratinocytes in stratum germinativum are attached to dermis layer by hemidesmosomes, keratinocytes within epidermis layer are strongly adhered to each other by desmosomes which partly accounts for the toughness of the epidermis as well as giving resistances to abrasions or preventing the ingress of foreign substances.

In this sublayer, tonofibrils fill nearly entirely the cytoplasm of keratinocytes. Tonofibrils surround the nucleus and then radiate toward the periphery, where it converge on desmosomes. Loops of tonofibrils at a desmosome is situated between adjacent keratinocytes and these binds actually form spined appearances.

Spinal shape appearance at desmosome resulted from aggregation of tonofibrils.

📌 3. Stratum Granulosum

Stratum Granulosum is known as a transition layer between metabolically active cells layer and dead cells layer. Keratinocytes in this layer are known as granular cells. In this layer, lamellar bodies and Kerahtohyalin granules are produced within the keratinocytes. Concurrent with the appearance of lamellar bodies and Kerahtohyalin granules, nuclei and most of the cytoplasmic organelles of keratocytes almost disappear, signs that herald formation imminently of a cornified layer/stratum corneum layer.

Keratohyalin granules contain proteins that involved in the aggregation of keratin filaments and in the formation of the cornified protein envelope. Meanwhile, lamellar bodies contain lipids and fuse with the plasma membrane in order to secrete its content called lamellae into the extracellular space and and eventually forms cornified lipid envelop.

Keratohyalin granule and lamellar body in keratinocyte.

The lamellae extruded by lamellar bodies consist of :

• Lipids (glucosylceramides, sphingomyelin, phospholipids, cholestrols)
• Lipid processing enzyme (beta-glucocerebrosidase which also known as glucosyceramidase, acid sphingomyelinase and secretory phospholipase) – to make upper layer waterproof
• Structural protein (corneodesmosin) – to optimise corneocytes cohesion
• Protease (kallikreins, cathepsins)
• Glycosidases and protease inhibitors (elafin, secretory leucocyte protease inhibitor, lympho-epithelial kazal-type-related inhibitor, alpha-2-macroglobulin-like) – to control desquamation
• Antimicrobial peptides (defensins, cathelicidin)

Keratohyalin granules primarily contain electron-dense protein which are profilaggrin and keratin intermediate filaments. Profilaggrin is stored in an inactive, insoluble and heavily phosphorylated form there.

During the transition of granular cells to corneocytes (keratinocytes without nuclei and cytoplasmic organelles), keratohyalin granules degranulate and profilaggrin is dephosphorylated and proteolysed in a multistep process forming free filaggrin monomers by a variety of proteases including matriptase, prostasin and kallikrein.

Then, these free filaggrin monomers bind directly to keratin intermediate filaments, causing their aggregation into macrofibrils in which the keratin intermediate filaments are aligned in tightly packed parallel arrays. This process contributes to cellular compaction and permits extensive crosslinking of keratin intermediate filaments by transglutaminases to form a highly insoluble keratin matrix. This matrix acts as a protein scaffold for the attachment of cornified protein envelope to cornified lipid envelope that together form the stratum corneum.

📌 4. Stratum Lucidum

Stratum Lucidum is the layer that only present in thicker skin of hand palms and feet soles. Its main function is to reduce friction between the Stratum Corneum and Stratum Granulosum. Keratinocytes in this layer are already died and flattened forming a clear layer. They are densely packed with eleiden, a clear protein rich in lipids derived from keratohyalin which responsibles for the transparent appearance and water barrier function.

📌 5. Stratum Corneum

Keratinocytes in stratum corneum are fully died, nuclei and all of the cytoplasmic organelles fully disappear. The cells are flattened, filled with keratin fibres and known as corneocytes or keratinized cells. Corneocytes adhere to each other by corneodesmosomes.

The contents extruded by lamellar bodies are modified by the action of the produced enzymes to generate ceramides, cholesterol, fatty acids and cholesterol ester that form lamellae between the corneocytes and embed the cornified protein envelopes in lipid envelopes.

In spite of promoting aggregation of keratin filaments, filaggrin also undergoes subsequent degradation by a variety of proteases into free amino acids and derivatives such as amino acid, urocanic acid (UCA), pyrrolidone carboxylic acid (PCA), lactate and urea.

Structure of corneocyte.

Illustration of stratum corneum layer.

As the top of cornified/keratinized layer getting old, corneodesmosomes are enzymatically cleaved and old corneocytes are slough off welcoming new corneocytes. This process refers to the desquamation or turnover process and regarded as defense. Amazingly, this process will be always repeated by the skin as long as the body still alive. Through this process, skin will always get new cornecytes cells on top and the unwanted substances are prevented to remain in the epidermis, all are discharged from the skin.

Sloughing of oldest corneocytes.