[CJC] Stem Cells (1.5) Lecture Notes

Page 1 | 20 CATHOLIC JUNIOR COLLEGE H2 Biology JC1 CORE IDEA 1] THE CELL AND BIOMOLECULES OF LIFE 1.5 STEM CELLS Narrative from H2 Biology 9744 Syllabus: This concept highlights the diversity in cell type and morphology in an organism. In an organism, all cells except the gametes are genetically identical. Yet, a liver cell, a rod cell in the eye and an epithelial cell in the ileum differ significantly in terms of morphology and function due to differential gene expression. The same genome gives rise to a wide range of cells which further forms tissues, organs and systems in an organism. The ability of stem cells to divide and their potential for self -renewal allows growth. Stem cells replace cells that die or are damaged. During embryogenesis, cell division and differentiation allow the development of an entire organism in utero from a single-cell zygote. Stem cells hold great potential as medical treatments. Haematopoietic stem cells are used in blood marrow transplants in cancer treatments. Skin stem cells may be used to culture skin cells to treat patients with massive burns. Ethical debates over the use of stem cells are primarily concerned with the use of embryonic stem cells. Use of adult stem cells faces fewer of such ethical issues. Candidates should be able to: Subtopic Learning Outcomes UNIQUE FEATURES OF STEM CELLS 1(t) Describe the unique features of stem cells , including zygotic stem cells, embryonic stem cells and blood stem cells (lymphoid and myeloid), correctly using the terms: i. totipotency (e.g. zygotic stem cells which have ability to differentiate into ANY cell type to form whole organisms and so are also pluripotent and multipotent), ii. pluripotency (e.g. embryonic stem cells which have ability to differentiate into ALMOST any cell type to form any organ and so are not totipotent but are multipotent) and iii. multipotency (e.g. lymphoid and myeloid stem cells which have ability to differentiate into a LIMITED range of cell type and so are not pluripotent or totipotent) NORMAL FUNCTIONS OF STEM CELLS 1(u) Explain the normal functions of stem cells in a living organism , including embryonic stem cells and blood stem cells (lymphoid and myeloid stem cells) ETHICAL IMPLICATIONS OF STEM CELL APPLICATIONS 1(v) Discuss the ethical implications of the application of stem cells in research and medical applications and how human induced pluripotent stem cells (iPSCs) overcome some of these issues. (Procedural details of how iPSCs are formed are NOT required.) CONTENT PAGE Concept Map 2 1 UNIQUE FEATURES of STEM CELLS 3 – 6 1.1 Unique Features of ALL Stem Cells 3 1.2 Development Potential of Stem Cells 1.2.1 Totipotency (e.g. zygotic stem cells) 1.2.2 Pluripotency (e.g. embryonic stem cells) 1.2.3 Multipotency (e.g. adult stem cells) 4 5 6 2 NORMAL FUNCTIONS of STEM CELLS 7 – 9 2.1 Embryonic Stem Cells 7 2.2 Adult Stem Cells: Blood Stem Cells (Haematopoietic Stem Cells) 8 – 9 3 ETHICAL IMPLICATIONS OF STEM CELL APPLICATIONS 10 – 17 3.1 Application of Stem Cells 10 – 11 3.2 Ethical Implications 12 – 14 3.3 Human Induced Pluripotent Stem Cells (iPSCs) 15 – 17 4 APPENDIX 18 - 20 4.1 Methods of Making iPSCs; Sigals for Differentiation (Blood Stem Cells); Transdifferentation 18 – 20

Page 2 | 20 CONCEPT MAP OF STEM CELLS (SC) DEVELOPMENTAL POTENTIALS OF STEM CELLS Types Zygotic SC (early ESC) Embryonic SC Fetal SC * (Umbilical) Cord SC Infant / Adult SC Source single-celled zygote; 2-celled to 8-celled stage (0-1 Day; 2 to 4/5 Days) Inner Cell Mass of blastocyst (5/6 Days to 6/7 Weeks) fetal tissues (after 8 Weeks) Umbilical Cord / Cord Blood; Placental Tissue 1. Neural SC 2. Cardiac SC 3. Bone Marrow SC Developmental Potential Totipotent Pluripotent Pluripotent or Multipotent Pluripotent or Multipotent Multipotent Normal Function able to differentiate into All cell types including those of extra-embryonic membranes to form the whole organism able to differentiate to MOST cell types except those of extra-embryonic membranes able to differentiate to MOST cell types or MULTIPLE but LIMITED RANGE of cell types able to differentiate to MOST cell types or MULTIPLE but LIMITED RANGE of cell types able to differentiate into MULTIPLE but LIMITED RANGE of cell types *including tetracarcinorma (or germ cell tumour) that may be found in the fetus

Page 3 | 20 1] UNIQUE FEATURES OF STEM CELLS 1.1 UNIQUE FEATURES OF ALL STEM CELLS 1. Stem Cells are able to PROLIFERATE INDEFINITELY • Stem cells has unlimited proliferative potential (divide many times through mitotic cell division), unlike differentiated cells which can only divide for a set number of replicative cycles. • Telomerase in stem cells is activated, hence their telomere do not shorten to a critical length that induce cell apoptosis. 2. Stem Cells are capable of SELF-RENEWAL • When a stem cell divides, one daughter cell remains as a stem cell while the other takes on a specialized function. • This ensures that the stem cells are always present for future cell divisions. 3. Stem Cells are UNSPECIALISED cells • There is an absence of tissue -specific structures, therefore, unable to perform specialised functions. 4. Stem Cells are capable of DIFFERENTIATION / SPECIALISATION under appropriate conditions • Stem cells respond to intracellular and extracellular signals to regulate the rate of cell division and gene expression by re- modeling of the chromosome. Cell differentiation is controlled at chromatin level. • The intracellular signals are controlled by the genes, which carries coded instructions for all the structures and functions of a cell. Genes that are required for specialized functions are activated by acetylation of histones or demethylation of DNA. • The extracellular signals are chemicals secreted by other cells , physical contact with neighbouring cell and certain molecules and compounds surrounding a cell in an organism. Fig. 1: Characterisitics of stem cells The developmental potential depends on the type of stem cells and the source from which the stem cells are extracted. Depending on the degree and extent of differentiation capability, stem cells can be described as either totipotent, pluripotent or multipotent.

Page 4 | 20 1] UNIQUE FEATURES OF STEM CELLS 1.2 DEVELOPMENTAL POTENTIAL (or CELL POTENCY) OF STEM CELLS CELL POTENCY: This describes a cell's ability to differentiate into other cell types. 1.2.1 TOTIPOTENCY • Totipotent Stem Cells have the ability to differentiate into ANY or ALL cell types, including cells of the extra-embryonic membranes, to form whole organisms. • Example: ZYGOTIC stem cells Fig. 2: The first diploid cell after fertilisation of the egg cell by sperm nucleus is the zygote. Fig. 3: Zygotic stem cells are derived from the first 4 or 8 cells produced by the cleavage / cell division of the zygote. Fig. 5: Zygotic stem cells are able to differentiate into any cell type of the extra- embryonic membranes comprising chorion, amnion, allantois, yolk sac, placenta Fig. 4: A blastocyst

Page 5 | 20 1] UNIQUE FEATURES OF STEM CELLS 1.2 DEVELOPMENTAL POTENTIAL (or CELL POTENCY) OF STEM CELLS 1.2.2 PLURIPOTENCY • Pluripotent Stem Cells have the ability to differentiate into any cell type, tissues or organs EXCEPT cells of the extra-embryonic membranes • Example: EMBRYONIC stem cells Embryonic stem cells are derived from the inner cell mass of the blastocyst. The blastocyst is a ball of cells about 5 days after fertilization, which gives rise to the embryo and ultimately the foetus. The blastocyst comprises : • INNER CELL MA