Cell differentiation_ part 2.pdf

05/10/23 Cell differentiation: part 2 Learning objective: understand key features of an example of differentiation cells that determine their specialised function. First example: colon ( colonic crypt ): The epithelial layer of the human colon consists of a single sheet of columnar epithelial cells...

05/10/23 Cell differentiation: part 2 Learning objective: understand key features of an example of differentiation cells that determine their specialised function. First example: colon ( colonic crypt ): The epithelial layer of the human colon consists of a single sheet of columnar epithelial cells which form crypts and villi. Stem cells are located at the bottom of the crypt. There are 4 terminally differentiation cell types in the colon that originate from a single multipotent stem cell through a number of committed progenitors: The colonocytes The mucus-secreting goblet cells Peptide hormone secreting entero-endocrine cells Paneth cells Stem cells at the bottom of the crypt are more affertiman Marta Proliferative. The ones at the top are less proliferative. is How is proliferation regulated: This is regulated by wnt signalling. The wnt ligand is produced by stromal cells at the bottom of the crypt. This ligand binds to the receptor on the membrane of the stem cells. On binding, a destruction complex of four molecules: GSK3, beta axin, ck1 and APC become inactivated. This inactivation releases beta catenin which then translocates to the cell nucleus where it acts as a transcription factor to activate genes such as cyclin D1, and this leads to proliferation. Higher up the crypt wnt ligand is not present, the destruction complex is active. It phosphorylates beta catenin tagging it for ubiquitination or protesmol degradation. This means the gene isn’t transcribed. Regulation of differentiation/ specialisation: colonic crypt Differentiation is controlled by notch signalling. Whether the notch is on or off determines the fate of the crypt based columnar cells ( CBCCs ). If notch signalling is on, the CBCCs differentiate to absorptive cell fates such as enterocytes. If notch signalling is switched off, the CBCCs differentiate to secretory progenitor cells, which differentiate into secretory cells such as: Paneth cells, goblet cells and enteroendocrine cells. Examples of differentiated cells: skin The skin contains 3 main layers. The epidermis, the dermis and the hypodermis. The epidermis is composed of self-regenerating strati ed attened epithelial cells, keratinocytes. The epithelial stem cells differentiate into keratinocytes. Keratinocytes form the outer protective layer of keratin composed of: Stratum corneum Stratum lucidum Stratum granulosum Stratum Spinosum Stratum basale There are three types of differentiated and specialised cells in epidermis with speci c functions: 1. Melanocytes: localised in the basal layer ( stratum basale ) Produce and secrete melanin using the tyrosinase gene Provide UV protection 2. Langerhans cells: Belong to monocyte lineage, similar to macrophages Involved in immune surveillance 3. Merkel cells: Belong to epithelial lineage Function as mechanoreceptors Main functions of the epidermis: 1. Protection: Stratum corneum: an anatomical barrier to pathogens. Stratum spinosum: immune defence Stratum basale: UV protection 2. Sensation: Stratum basale: via merkel cells 3. Control of evaporation: Semi-impermeable barrier to uid loss 4. Storage and synthesis: Stratum basale and spinosum synthesis vitamin D 5. Absorption: Oxygen supply to outermost layer of skin Administration of medicines ( ointments and adhesive paths ).