Download Maintenance of the Skin through Cell Differentiation –

Julie Ji
BE 553
04/09/01
Maintenance of the Skin through Cell Differentiation –
Nature’s Way of Engineering Tissues
Julie Ji
Tissues in one’s body are continuously being created, maintained, remodeled, regenerated, and
reabsorbed through carefully designed programs of processes such as cell proliferation, migration,
differentiation, and cell death. These processes are carried out in an orderly and timely fashion, as
suitable to the needs of the organism, under the direction of a complex network of signals, both
biochemical and mechanical. From cell differentiation during development, to skin and muscle
regeneration during wound healing, to nerve end extensions, Nature is full of elegant examples of
engineering tissues with both precision and efficiency.
Different types of tissues in a body consist of different kinds of cells. Some tissues, such as nerve
and heart muscle, are made of permanent cells that once lost are lost forever. At the other extreme, cells
such as liver and endothelial cells that line the blood vessels are replaced through cell division. There are
yet some tissues made of cells derived directly from stem cells: cells that are not yet terminally defined in
their functions and have the ability to differentiate into any type of cells in the body. One example is the
skin. Maintenance of such a tissue in direct contact with the external environment is accomplished by the
body through an organized process of stem cell differentiation. A careful examination into the life of a
skin cell provides a powerful illustration of Nature’s way of tissue engineering based on the principle of
cell differentiation.
The skin, or the epidermis, is composed of many layers of cells that vary in shape and other
characteristics corresponding to their stage of differentiation. As the cells differentiate, they travel
perpendicular to the sheet of stem cells from which they originate and move toward the outside of the
skin. At the innermost layer of skin is an underlying basal lamina made up of the stem cells for the skin.
These cells tend to have a round, spherical shape. Right above the basal cells is a layer of prickle cells.
These cells are connected to each other through bundles of keratin filaments, hence the prickled look.
Keratin is the main structural protein of the skin. At this level, skin cells are metabolically active and are
Julie Ji
BE 553
04/09/01
thus submerged in open channels that allow for nutrient diffusion. Unlike basal stem cells, prickle cells
are beginning to show signs of becoming an epidermal cells in the increased presence of keratin filament.
At the outer edge of prickle cell layer is the granular cell layer. These cells appear granular
because they contain keratohyalin. Keratohyalin, composed mainly of the filaggrin protein, is thought to
aid in keratin cross-linking and intracellular compaction. Production of the keratin protein is also
elevated in granular cells, which have a markedly flattened shape and secrete a sealant material that
creates a waterproof barrier. The granular cell layer marks the separation of the actively dividing and
differentiating cells inside from the outside layers of flattened dead cells that have lost their intracellular
organelles. Granular cells are thus further differentiated from prickle cells in that they have a even more
distinct, flat, appearance and serve the more specified function of producing keratin.
Cells further beyond the granular cell layer begin to lose their nuclei and other cytoplasmic
organelles and are turned into squames, or flattened scales of the outer skin layer densely packed with
keratin. The cell membrane of the outermost granular cells and cells further up are reinforced by a tough,
cross-linked layer of intracellular protein called involucrin. Eventually, only tough protein filaments such
as keratin and involucrin are left in the shells of dead skin cells. These finally are shed off from the body,
turning into household dust.
So, skin cells are continuously being developed from the inner most basal layer of stem, which is
the only site of active cell division as stem cells make up for differentiated cells. Through interactions
with the biochemical environment created by neighboring cells, skin cells develop certain characteristics
such as cell shape and anchorage dependence specific to their state of differentiation. Cells begin the
production of proteins such as keratin and involucrin once they reach a specific level of differentiation.
Because the dead cells on the outermost layer are being continuously shed off, skin cells must be
constantly replenished from the inside out, in an endless cycle of stem cell division, skin cell
differentiation and cell death.