Cell Differentiation PDF

HPP Human Physiology and Pharmacology (HPP) “Organization of the body and Cell Differentiation” Prepared by Dr. Shaymaa ElBahy & Dr Nour Abdelkader Extracted from Dr Bayissi Bading-Taika Learning Outcomes At the end of the lecture and your own independent study you sh...

HPP Human Physiology and Pharmacology (HPP) “Organization of the body and Cell Differentiation” Prepared by Dr. Shaymaa ElBahy & Dr Nour Abdelkader Extracted from Dr Bayissi Bading-Taika Learning Outcomes At the end of the lecture and your own independent study you should: ◼ Explain the theory and process of cell differentiation. ◼ Briefly describe embryonic development ◼ Describe the control of differentiation ◼ Describe cell renewal and give examples of specialised cells. ◼ Describe differentiated cells ◼ Define stem cells. Recap Human Body Cells Organ Organ Systems Tissues Multi-cellular Community Bone Reproductive Epithelium Skin Blood Nerve cells Muscle All cells originate from one cell.........created at the point of fertilisation  Embryonic development The zygote divides -> to two then –> four then-> eight cells After three divisions cells begin to differentiate towards different functions. How did scientists realize this fact? Cell commitment to differentiation Cells can removed from an early blastocyst during IVF for genetic testing. If cells are removed after 3 divisions (8 cells) it can be fatal to the embryo This shows us that it is at this point the cells become committed to a particular fate, and cannot be replaced by others after they have been removed. www.advancedfertilit y.com/embryos.htm  The early blastocyst and genetic testing  Prenatal genetic screening  Prenatal genetic diagnosis Measures risk of genetic disease Confirms a genetic condition Non-invasive Invasive Involve blood test or ultrasound Method used: imaging amniocentesis and Screens for: chorionic villus sampling aneuploidy; Diagnosis for: defects of the brain and spine called positive aneuploidy screening neural tube defects (NTDs), results, some defects of the abdomen, known family history of genetic heart, and facial features. disorders, or anomalies identified on ultrasound. Embryonic Stem cells Pools of stem cells persist in several adult tissues As the embryo grows, most cells become increasingly restricted in their developmental potential Totipotent up to division three, can become any cell including placenta Pluripotent embryonic stem cells those found in the blastocyst, can become any cell of the body except placenta. Multipotent adult stem cells, less versatile, more specialised, potential to give rise to some tissues and finally mature into specialised/differentiated cells Potency ◼ There are different types of stem cell ◼ Stem cells that produce any type of cell are described as totipotent, this includes placental cells ◼ A zygote, the cell formed after fertilisation, is the first stem cell of a developing body ◼ The first few cells formed through the first two cell divisions are also totipotent ◼ After this embryonic stem cells become pluripotent. They can still specialise into any cell in the body, but they lose the ability to become the cells that make up the placenta  Potency ◼ Stem cells present in adult mammals are either: ◼ Multipotent - able to differentiate into a few different types of cell. Example of this are neural stem cells found in the adult brain or haematopoietic stem cells in the bone marrow which give rise to different blood cells (red and white blood cells and platelets) ◼ Unipotent - can only differentiate into one cell type e.g. epidermal skin cells, that make up the outer layer of your skin Embryo Differentiation and migration of cells  Endoderm: inner lining of embryonic germ layer, gives rise to internal structures like epithelial cells  Mesoderm: middle lining of embryonic germ layer, gives rise to bones  Ectoderm: outer part of embryonic germ layer, gives rise to skin, nervous tissue  Embryonic Cell Differentiation Ectoderm Divide and differentiate over many generations Embryonic Cell Mesoderm differentiation Divide and is how generic differentiate over many embryonic cells generations become specialized cells Endoderm Divide and differentiate over many generations  The DNA information carried in the zygote is identical to the DNA found in mature specialised cells. How did scientists realize this  First mammal to be cloned fact? from adult cell  demonstrated that the DNA specialised cells can be used to create an entire organism.  Therefore fully differentiated Dolly the sheep specialised cells contain a complete set of DNA.  Making Dolly Surrogate 1 2 mother Hormones to trigger ovulation Egg cell Udder cell donor donor Nucleus removed Enucleated Fusion via udder cell from ovum electroporation Enucleated egg Nucleus cell Implanted into surrogate at blastocyst stage Dolly born fertile and 1 genetically identical to 2 2 the mother, who donated somatic DNA What Is the Source of New Cells for Tissues? ◼ Inside every tissue, cells are constantly replenishing themselves through the process of division, although the rate of turnover may vary widely between different cell types in the same tissue. ◼ For example, in adult mammal brains, neurons rarely divide. However, glial cells in the brain continue to divide throughout a mammal's adult life. ◼ Mammalian epithelial cells also turn over regularly, typically every few days. 16 What Is the Source of New Cells for Tissues? ▪ Many differentiated cells lose the ability to differentiate thus tissues maintain stem cells to serve as a reservoir of undifferentiated cells. ▪ Hormones ex EPO signals erythropoiesis in bone marrow ▪ Transcription factors (proteins that regulate which genes are transcribed in a cell ) determine the pathway particular stem cells take as they differentiate. ▪ For example, both intestinal absorptive cells and goblet cells arise from the same stem cell population, but divergent transcriptional programs cause them to mature into dramatically different cells 17 Properties of stem cells ◼ It is not terminally differentiated (not at the end of a pathway of differentiation) ◼ It can divide without limit (or at least for the lifetime of the animal) ◼ When it divides, each daughter has a choice: it can either remain a stem cell, or it can embark on a course leading irreversibly to terminally differentiation 19 11/1/2024  Hox Genes (Homeotic genes)  Hox genes are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals (control layout of the embryo anterior - posterior axis)  Edward Lewis work on fruit flies in 1978 discovered a mutation in the Antennapedia gene causes fruit flies to develop legs in place of antennae on the head segment. In humans: Mutations in PAX hox genes result in anatomical disorders of the eye and Mutation in MSX hox genes result in abnormal face, head and tooth formation. Hox genes (responsible for the layout)  Schematic representation of gene expression patterns of Drosophila HOX genes.  Hypothetical construction of human HOX genes (extrapolated from data in the mouse).  Knowledge comes from gene targeting studies on Adapted from Homeobox Genes in Embryogenesis and Pathogenesis mice. Manuel Mark, Filippo M Rijli and Pierre Chambon Differentiated cells are different from stem cells in: they synthesise specific proteins….. ◼ Red blood cells: Synthesise Haemoglobin To transport oxygen around the body ◼ Differentiated muscle cells synthesise actin and myosin proteins for contraction ◼ Pancreatic Beta cells: Produce insulin For secretion into the blood Differentiated cells take on characteristic shapes Nerve cells develop long axons to connect the nervous system Fat cells are round and grow as they store fat Differentiated cells develop cytological structures specific to their role. Melanocytes develop dendritic tentacles That deliver melanin into surrounding cells Tentrillioncellhuman.co Epithelial cell of the small intestine develop microvillus to increase the absorptive surface area. © science photo library Growth and Cell Renewal After embryonic differentiation there is still a requirement for growth, regeneration and repair Tissue architecture is preserved despite constant replacement of old cells with new ones Rates of renewal vary and may change Cell renewal by stem cells ◼ Terminally differentiated cells that are unable to divide are continuously replaced by stem cells. ◼ These are usually cells with short lifespans in harsh environments ◼ Examples of these tissues are skin and blood cells (differentiated and have limited ability to divide)  Gut epithelium renewal by stem cells Single layered epithelium in small intestine Villi and crypts Location of stem cells – in the depth of the crypt, protected Dividing and non dividing cells Cells move upwards, die at the tip of the villi, shed into the lumen Cycle time: 3-5 days  Cell renewal by stem cells - epidermis Multilayered epithelium Cells change appearance from one layer to the next Basal cells – prickle cell layers – granular cell layer – keratinized squames Epidermis stem cells – subset of basal cells – immortal stem cell Cycle time 2-4 weeks Regulated according to the thickness of the epidermis Renewal of blood cells Erythrocytes - red blood cells Lymphocytes Neutrophils All very different but originate from the same stem cell in the bone marrow Renewal of blood cells by stem cells  Cell renewal by simple duplication ▪ Liver cells ▪ Normally renewed very slowly; stimulated by damage ▪ Endothelial cells ▪ Normally renewed very slowly (life span months or even years); can also grow new capillaries (angiogenesis) Living donor Liver Transplant A section of the liver is removed from a living donor. Both livers regrow to the required volume within a year Reasons for liver transplant e.g. cancer, alcohol abuse, liver-specific metabolic diseases Cells that do not renew Nervous System Some cell don’t renew over your lifetime or renew very slowly: Nerve cells once differentiated are so specialised no longer divide Strict growth inhibition to control the complex system ©Livescience.com We can culture cells Quick activity: Put these cells in the correct order for the pathway of differentiation from the zygote to a mature hepatocyte. Decreasing developmental potential or potency Lineage and potency Can Can become Can Can Can become Can only become hepatocyte become become any cell of remain any liver or biliary any cell any cell in the liver hepatocyte stomach or cell epithelial cell the gut pancreas Early Foregut Mature Endoderm Liver Hepatoblast blastocyst endodermal Hepatocyte cell stem cell cell stem cell Decreasing developmental potential or potency Activity 2 Capable Characteristics of stem cells Characteristics of differentiated cells of infinite division. Specialised proteins e.g. keratin Irregular shape to aid function Large nucleus Loss of Unremarkable nucleus shape  Characteristics Characteristics of of stem cells terminally differentiated cells Specialised Large proteins nucleus e.g. keratin Capable of infinite Irregular shape division to aid function. Unremarkable shape Loss of nucleus  Summary This lecture is about the concepts you are not expected to know examples in detail. ▪ Key concepts ▪ Large variety of specialized cells in the human body ▪ Product of a process of gradual commitment. The final step in cell specialization, called cell differentiation ▪ Change from being totipotent to pluripotent to multipotent to, finally, specialized cells ▪ Cell memory and signals from the neighbours keep them different ▪ They collaborate to form tissues. Tissues join together in different combinations to for organs, which perform a variety of functions Reading ▪ Scitable by Nature Cell Differentiation and Tissue ▪ https://www.nature.com/scitable/topicpage/cell- differentiation-and-tissue-14046412 ▪ Further reading ▪ https://www.nature.com/scitable/topicpage/gene- expression-regulates-cell-differentiation-931 ▪ Embryo development The principles of human Physiology. 5th or 6th Edition C.L. Stansfield. (the book recommended for the module) Example Hormones IGF growth factors (insulin like growth factors) stimulate mitosis and growth and regulate metabolism. Autocrine and paracrine actions of growth hormones even before the pituitary and thyroid glands have formed. Fetal glucocorticoid stimulates final maturation in the cells of the lungs, liver and intestines  Example Growth factors Epidermal growth factor- binds to the EGFR receptor of cells to promote proliferation. Transforming growth factors (sometimes called Tumor growth factors) more than 30 Fibroblast Growth factors 20 different types Embryonic cholinesterase appears early stage of development. It disappears from the embryonic cells after they have assembled into definite organ structures. Embryo Differentiation and migration of cells 43  Stem cells have been used in a number of degenerative eye conditions to build new tissues with success and now trials have been successful, example in Stem cell treatment for age-related macular degeneration From embryonic stem cells and from some adult stem cells like the haematopoietic stem cells.  Asymmetric Cell division ▪ Whenever stem cells are called upon to generate a particular type Different of cell, they undergo progeny an asymmetric cell division. ▪ In this case, one of the daughter cells has a finite capacity for cell division and begins to differentiate, Cell matures Divides whereas the other daughter cell remains a stem cell with unlimited proliferative ability. Occurs more during embryonic development Symmetrical Division Cell divides External factors drive differentiation during maturation More common in later growth and renewal