PJ1311 Lecture 1 - Cell Renewal PDF

The Human Body PJ1311 Lecture 1: Cell Renewal Dr Alina Oknianska Learning Objectives and Exam Revision Advice You should be able to discuss stem cell (SC) function and different types of stem cells and understand medical applications of SC  Introductio...

The Human Body PJ1311 Lecture 1: Cell Renewal Dr Alina Oknianska Learning Objectives and Exam Revision Advice You should be able to discuss stem cell (SC) function and different types of stem cells and understand medical applications of SC  Introduction Cell proliferation and death balanced throughout life of multicellular organism  Introduction Development begins with rapid proliferation of embryonic cells Differentiate to produce specialised cells – adult tissues and organs  Introduction Human body 1014 cells – 200 differentiated cell types Originate d from single cell  Introduction As cells differentiate – rate of proliferation decreases Cells arrest in G0 of cell cycle  Introduction BUT cells lost due to injury or programmed cell death Need to maintain cells in adult tissues and organs Tissues contain cells able to proliferate – replace cells Some tissues have high rate of turnover Subpopulation continuously dividing  Proliferation of Differentiated Cells What happens if these cells need to be replaced? Some differentiated cells retain ability to divide Re-enter the cell cycle Most differentiated cells unable to proliferate Proliferation of less differentiated cells  Proliferation of Differentiated Cells Some differentiated cells retain ability to divide Fibroblasts – connective tissue Skin fibroblasts Endothelial cells blood vessels Some internal organs e.g. liver  Proliferation of Differentiated Cells : Fibroblasts Skin fibroblasts normally arrest in G0 Rapidly proliferate if need to repair damage – cut or wound Blood clotting release of PDGF from platelets Stimulates proliferation and migration of fibroblasts Repair and regrowth of damage tissue  Proliferation of Differentiated Cells : Endothelial Cells Endothelial cells also remain capable of proliferation Form new blood vessels for repair and regrowth of damaged tissue Release of VEGF (low oxygen) Stimulate cell proliferation and outgrowth of new  Proliferation of Differentiated Cells : Endothelial Cells Liver Regeneration Liver cells in G0 Remove part of liver Remaining cells proliferate to regenerate liver  Proliferation of Differentiated Cells : Endothelial Cells Capable of resuming cell proliferation Smooth muscle cells (walls of large blood vessels) Contractile portions of digestive and respiratory tract Other internal organs Unable to divide Differentiated skeletal muscle  Proliferation of Differentiated Cells What happens if these cells need to be replaced? Some differentiated cells retain ability to divide Re-enter the cell cycle Most differentiated cells unable to proliferate Proliferation of less differentiated cells self-renewing stem cells  Stem Cells Most fully differentiated cells unable to divide – terminally differentiated Replaced by proliferation of subpopulation of less differentiated self-renewing cells Stem cells  Stem Cells Stem cells have critical role in maintenance of most tissues and organs Capacity to proliferate Replace differentiated cells throughout lifetime of an animal  Stem Cells Key property of stem cells One stem cell divides to produce one cell – stem cell one cell – divides and differentiates  Stem Cells Stem cells are self-renewing populations Source of differentiated cells throughout life Key role in tissues where cells have short life spans Blood cells Epithelial cells of skin Epithelial cells of digestive tract  Stem Cells First identified in 1961 by McCulloch and Till Hematopoietic (blood-forming) system Single cell from mouse bone marrow proliferate and differentiate into multiple blood cells Hematopoietic stem cells well characterised  Hematopoietic Stem Cells (HSCs) Several distinct types of blood cells  Hematopoietic Stem Cells (HSCs) All blood cells have limited life spans Less than one day to few months Over 100 billion blood cells lost every day in humans – continually replaced All blood cells derived from same population of HSCs in bone marrow  Hematopoietic Stem Cells (HSCs) Descendants of HSCs continue to proliferate Committed to specific differentiation pathways Influenced by factors Hematopoietic Stem Cells (HSCs)  Intestinal Stem Cells Example of stem cells in self renewal of epithelial tissue Intestine lined with single layer of epithelial cells Digestion of food and absorption of nutrients  Intestinal Stem Cells Intestinal epithelial cells exposed to harsh environment Lifetime only few days before die and shed into digestive tract Renewal of intestinal epithelium continual process throughout life New cells formed from continuous (but slow division) of SCs at bottom of intestinal crypts  Intestinal Stem Cells SCs give rise to transit-amplifying cells – divide rapidly  Intestinal Stem Cells Transit-amplifying cells proliferate for 3 – 4 cell divisions Differentiate into 3 cell types of colon surface epithelium  Intestinal Stem Cells Each crypt contains approx. 6 self-renewing SCs  Skin Stem Cells SCs responsible for continuous renewal of skin and hair Skin and hair exposed to harsh external environment E.g. UV radiation from sunlight Cells continuously renewed through life  Skin Stem Cells Skin consists of 3 major cell lineages Epidermis Hair Follicles Sebaceous glands Releases oils – lubricate skin surface https://www.dreamstime.com/royalty- free-stock-photo-skin-cross-section-  Skin Stem Cells Each cell line maintained by own SCs Epidermis is a multilayer epithelium Turnover every 2 weeks Cells replaced by epidermal SCs in single basal layer SCs give rise to transit-amplifying cells – several divisions in basal layer Differentiate and move outward to surface  Skin Stem Cells Renewal of the epidermis by stem cells  Skin Stem Cells Each cell line maintained by own SCs Hair produced from stem cells in hair follicle Located in the bulge  Skin Stem Cells Cells to form hair shaft Hair produced from SCs in hair follicle Bulge SCs give rise to transit- amplifying cells Transit-amplifying cells proliferate and differentiate to form the hair shaft  Skin Stem Cells Each cell line maintained by own SCs Sebaceous gland cells produced from SCs Located at the base of sebaceous gland Skeletal Muscle Stem Cells Role of SCs in repair of damaged tissue Skeletal muscle composed of large multinucleated cells (muscle fibers) Formed by cell fusion during development  Skeletal Muscle Stem Cells Skeletal muscle normally a stable tissue – little cell turnover Regenerate rapidly in response to injury or exercise Regeneration from muscle SCs – satellite cells Located in basal  Skeletal Muscle Stem Cells Satellite cells normally arrested in G0 Activated to proliferate in response to injury and exercise Activated satellite cells give rise to progeny Undergo several divisions Differentiate and fuse to form new muscle fibers Skeletal Muscle Stem Cells  Medical Applications of Adult Stem Cells Ability to repair damaged tissue – potential clinical use Replace damaged tissue and treat variety of disorders Diabetes or degenerative diseases e.g. muscular dystrophy, Parkinson’s or Alzheimer’s disease Well established clinical application  Medical Applications of Adult Stem Cells http://healthcare-treatment.com/wp-content/uploads/2016/06/Stem-Cell-Therapy-for-  Types of Stem Cell Adult SCs that renew organs are multipotent Cells differentiate and give rise to many but limited cell types E.g. hematopoietic SCs can produce different types of blood cell can’t produce a brain cell  Types of Stem Cell Embryonic SCs are pluripotent Cells differentiate and give rise to any cell types  Types of Stem Cell Induced pluripotent SCs (iPS cells) Adult somatic cells converted to pluripotent SCs Types of Stem Cell: Summary  Types of Stem Cell: Summary Type of SC Derived from Type Adult tissue, Adult SCs Multipotent organs or blood Embryonic SCs Blastocyst Pluripotent Induced Reprogrammed Pluripotent Pluripotent SCs somatic cells  Types of Stem Cell: Summary Type of SC Derived from Type Zygote SC Zygote Totipotent