YIJC [H2] CI1.5 Stem Cells (N)

2024 JC1 BIOLOGY LECTURE NOTES CORE IDEA 1: THE CELL AND BIOMOLECULES OF LIFE TOPIC 1.5: STEM CELLS Learning Outcomes: (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) ii. pluripotency (e.g. embryonic stem cells) iii. multipotency (e.g. lymphoid and myeloid stem cells) (u) Explain the normal functions of stem cells in a living organism, including embryonic stem cells and blood stem cells (lymphoid and myeloid) (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). Use the knowledge gained in this section in new situations or to solve related problems. References: Reece, J. B. et al. (2018). Campbell Biology (11th Ed). Chapter 19: DNA Technology, pp. 460 – 465. Note: This textbook is available in our library. You may wish to borrow the book to supplement your reading when necessary. H2

2 1. What are Stem Cells? 1.1 Definition The stem cell is an undifferentiated and unspecialised cell that can divide over long periods and can produce specialised cell types in the body. 1.2 Properties All stem cells are different from other cells in the body in three main ways: 1. Stem cells are undifferentiated and unspecialised. • They do not have any tissue -specific structures that allow them to perform specific functions. o E.g. stem cells do not produce haemoglobin to carry oxygen through the bloodstream like a red blood cell • However, unspecialised stem cells can differentiate to become specialized cells, e.g. red blood cells. 2. Stem cells are capable of long-term self-renewal. • Stem cells can divide and produce copies of themselves (i.e. proliferation), to replenish their cell count. • Stem cells undergo mitotic division to produce two genetically identical daughter cells via: o symmetrical division which form 2 daughter stem cells o asymmetrical division where one daughter cell remains a stem cell while the other daughter cell becomes a progenitor cell which undergoes further division and differentiate into other specialised cell types. o A progenitor cell is a n immediate descendent of a stem cell that is fate-restricted. E.g. progenitor daughter cells of haematopoietic stem cells can only differentiate into various blood cell types (e.g. red blood cells, mast cells, neutrophils) and not other cell types. Fig. 1.1 Types of cell division in stem cells

3 Fig. 1.2 Division and differentiation of progenitor cell 3. Stem cells can differentiate. • Stem cells have the potential to become other more specific cell types. These new cells used to replace damaged or diseased cells of the tissues and organs in the body. • Once stem cells have differentiated to form progenitor cells , they have fate restricted and become ‘committed’ to becoming a particular cell type. o E.g. skin stem cells give rise to new skin cells when needed, to assist regeneration after damage and as part of the normal ageing process. These new skin cells are committed to the role of skin cells and do not play other roles. • Stem cells can be triggered to differentiate by: o internal signals like presence / availability of different transcription factors. o external signals like chemicals secreted by other cells, physical contact with neighbouring cells or certain molecules in the cell's environment like growth factors. • These signals result in differential gene expression i.e. certain genes become activated and other genes become inactivated. As a result, a differentiated cell develops specific structures and performs specific functions. (Recall: Concept on D ifferential gene expression in CI2.4- 2.5:Organisation of Eukaryotic Genomes & Control of Eukaryotic Gene Expression.) E.g. a mature, differentiated neurone has dendrites and axon that receive and send nerve signals.

4 2. Types of Stem Cells Learning outcome (t): Describe the unique features of zygotic stem cells, embryonic stem cells and blood stem cells, correctly using the terms totipotency, pluripotency and multipotency. Stem cells can be categorised by • potency of the cell i.e. ability of the stem cell to differentiate into different cell types • origin / source of where the stem cells are obtained from The higher the potency, the greater the ability of the stem cells to divide into more types of specialised cells. Fig. 2 The type of stem cells and their potential to develop.

5 A) Totipotent stem cells • can differentiate into any cell type in the adult body , including cells that form the extraembryonic tissues (e.g. the placenta) needed for the development of the embryo,. • Totipotent cells are found in the zygote as well as cells produced within the first 3 mitotic divisions (i.e. up to the 8-cell stage of embryonic development). Fig. 2.1.1 Development of the Preimplantation Blastocyst in Humans B) Pluripotent stem cells • can differentiate into all cell types that develop to form the three germ layers (ectoderm, mesoderm and endoderm) (Fig. 2.1.2) but not cells that form the extraembryonic tissues. • Pluripotent stem cells are found in inner cell mass of the blastocyst (early human embryo).

6 Fig. 2.1.2 The 3 germ layers of an embryo (ectoderm, mesoderm and endoderm) that eventually give rise to the different types of tissues and organs in the adult. C) Multipotent stem cells • Can differentiate into multiple but limited number of related cell types. • found among differentiated cells in a tissue or organ, e.g. bone marrow, intestinal tract, skin • E.g. Haematopoietic (blood) stem cells in the bone marrow can differentiate into all the cells of the blood, such as red blood cells, white blood cells and platelets etc., but not other cells from a different tissue like neurones. • Research has also been shown that ASCs can differentiate into cells of a different lineage when appropriate chemical signals are provided in -vitro, e.g. haematopoietic stem cells can produce neurones. This property is known as plasticity.

7 Fig. 2.1.3 Multipotent stem cells Fig. 2.1.4 Summary of different levels of potency. Pluripotent embryonic stem cells c an differentiate into all the adult body cell types except cells that form extraembryonic membranes. Multipotent adult stem cells e.g. blood stem cells, c an only differentiate into a limited number of related specialised cell types. Totipotent zygotic stem cells c an differentiate into all the adult body cell types including extraembryonic membranes.

8 Fig. 2.2.3 Comparing ESC and ASC

9 3. Function of Stem Cells Learning outcome (u): explain the normal functions of stem cells in a living organism, including embryonic stem cells and blood stem cells (lymphoid and myeloid) 3.1 Embryonic Stem Cells • Embryonic stem cells (ESCs) play a crucial role in the early development of a living organism. • ESCs are derived from the inner cell mass of the blastocyst, which is a pre-implantation stage embryo around 4-5 days after fertilization. • ESCs are pluripotent, meaning they can differentiate into any cell type of the three primary germ layers - endoderm, mesoderm, and ectoderm. • Key Functions o Formation of the Embryo: The pluripotent ESCs in the inner cell mass of the blastocyst give rise to the entire body of the organism, including all specialized cell types and organs such as the heart, lungs, skin, and reproductive cells. o Differentiation into Germ Layers: As the blastocyst implants in the uterus, the ESCs begin to differentiate and form the three embryon