4BBY1030 Cell Biology and Neuroscience_Dec 2022 copy.pdf

Institute of Psyhology, Psychiatry and Neuroscience December 2022 Dr Brenda Williams Basic and Clinical Neuroscience 4BBY1030 Cell Biology and Neuroscience Stem Cells Part 1 Types of stem cells & their characteristics December 2022 Dr Brenda Williams Topic title: Stem Cells 2 Types of Stem Cells Fer...

Institute of Psyhology, Psychiatry and Neuroscience December 2022 Dr Brenda Williams Basic and Clinical Neuroscience 4BBY1030 Cell Biology and Neuroscience Stem Cells Part 1 Types of stem cells & their characteristics December 2022 Dr Brenda Williams Topic title: Stem Cells 2 Types of Stem Cells Fertlised egg Totipotent Can make extra-embryonic tissue, the embryo itself, all the tissues and organs of the body Zygote Morula Blastocyst Embryonic stem cells Pluripotent Gives rise to tissue stem cells for all three germ layers: endoderm, mesoderm, and ectoderm Tissue stem cells Multipotent Give rise to cell types of a specific tissue Adult tissue stem cells Hematopoetic SCs Neural SCs Mesenchymal SCs Cell types of a specific tissue Blood cells December 2022 Dr Brenda Williams Cells of the nervous system Topic title: Stem Cells Connective tissue, bone Cartilage, fat etc 3 Stem cells are non-specialised cells with specific characteristics Differentiate Self -renew December 2022 Dr Brenda Williams Topic title: Stem Cells 4 Characteristics of stem cells provide us with the potential to: Understand early human development (infertility, birth defects) Understand control of cell division (cancer) Cell-based therapies o Reduce need for organ and tissue donors/transplants o Replace mutant or damaged cells for treatment of diseases such as Parkinson’s disease, spinal cord injury, muscular dystrophy, heart disease, liver dysfunction, osteoporosis, vision and hearing loss Cell based drug screening platform December 2022 Dr Brenda Williams Topic title: Stem Cells 5 Part 2 Embryonic Stem (ES) cells December 2022 Dr Brenda Williams Topic title: Stem Cells 6 ES cells - Where do they come from? Inner cell mass egg fertilised egg 2-cell stage 8-cell stage Morula blastocyst Day 4-5 Human ES cells are derived from donated excess IVF embryos December 2022 Dr Brenda Williams Topic title: Stem Cells 7 ES cells - in the laboratory Can be grown indefinitely in the laboratory. Have potential to generate all cell types in our body (pluripotent). differentiation can be controlled/ manipulated in culture to generate specific cell types. MEFs December 2022 Dr Brenda Williams Topic title: Stem Cells 8 Ensuring cultured cells are embryonic stem cells - 1 Ensures cells are capable of long-term self-renewal Isolated ICM cells inspect cells through a microscope to see if look healthy and undifferentiated. Cells dissociated and replated Repeat dissociation and replated December 2022 Dr Brenda Williams Topic title: Stem Cells Irradiated MEFs New feeder layer 9 Ensuring cultured cells are embryonic stem cells - 2 Karyotyping Expression of pluripotency markers Oct4, NANOG, SOX2 NANOG Oct4 NCI Visuals Online DAPI December 2022 Dr Brenda Williams Topic title: Stem Cells AbCam ESI BIO 10 Ensuring cultured cells are embryonic stem cells - 3 Differentiation Spontaneous differentiation into cells of the three germ layers Remove Feeder cells Cultured ES cells Aggregation to form Embryoid body Subculture in lineage-specific differentiation conditions Transplantation into mice Teratoma formation December 2022 Dr Brenda Williams Topic title: Stem Cells 11 ES cells: Challenges Defining conditions for differentiation grow itio cond r e d un grow under cond iti embryonic stem cells grow un gro w un skin ns A ons B der c on d i de rc on neurons tions C blood dit i on sD liver December 2022 Dr Brenda Williams Topic title: Stem Cells 12 ES cells can give rise to all tissues ES cells from a black mouse Inject into host blastocyst from albino mouse December 2022 Dr Brenda Williams Topic title: Stem Cells 13 Part 3 Tissue Stem Cells December 2022 Dr Brenda Williams Topic title: Stem Cells 14 Function of tissue stem cells Generate tissues of the body during development Retained in adult tissues where they are involved in repair and replacement Bone marrow stem cells Haematopoietic stem cells Neural stem cells Includes stem cells isolated from fetal and cord blood Skin Stem cells Liver stem cells Muscle stem cells Examples of tissue stem cells and what they generate: December 2022 Dr Brenda Williams Topic title: Stem Cells 15 Haematopoietic stem cells (HSCs) Committed Progenitor cells Specialised cells December 2022 Dr Brenda Williams Topic title: Stem Cells 16 Mesenchymal stem cells (MSCs) Differentiation along specific lineages December 2022 Dr Brenda Williams Topic title: Stem Cells 17 Neural stem cells (NSCs) December 2022 Dr Brenda Williams Topic title: Stem Cells 18 Two neurogenic regions in the adult brain Subventricular zone (SVZ) lining the lateral ventricles Sensory information associated with olfaction (smell) Memory Striatum Subgranular zone (SGZ) of the hippocampal dentate gyrus Spacial learning memory Pattern separation Cognitive flexibility Memory clearance Mood Ertaylan et al. (2014): http://dx.doi.org/10.3389/fncel.2014.00437 December 2022 Dr Brenda Williams Topic title: Stem Cells 19 Summary of basic stem cell characteristics Stem cell committed progenitors: December 2022 Dr Brenda Williams Topic title: Stem Cells specialized cells: 20 The stem cell niche Microenvironment around stem cells that provides support and signals regulating self-renewal and differentiation December 2022 Dr Brenda Williams Topic title: Stem Cells 21 Part 4 Reproductive cloning and induced pluripotent stem cells December 2022 Dr Brenda Williams Topic title: Stem Cells 22 Reproductive cloning and stem cell research December 2022 Dr Brenda Williams Topic title: Stem Cells 23 The pluripotency factors The Yamanaka factors OCT4 SOX2 KLF4 C - MYC December 2022 Dr Brenda Williams Topic title: Stem Cells 24 Induced pluripotent stem cells Keratinocytes Hair root shaft cells Transduce with OCT4, SOX2, KLF4, cMYC Similar properties to embryonic stem cells Induced pluripotent stem cells (iPSCs) December 2022 Dr Brenda Williams Bypass ethical issues Topic title: Stem Cells 25 iPSCs: mechanism, transplantation, drug discovery December 2022 Dr Brenda Williams Topic title: Stem Cells 26 Some current applications of stem cells Treat blood diseases Tissue Stem Cells Umbilical cord stem cells Leukaemia in children Treat burns Repair corneal damage limbal stem cells (cornea) iPSC derived retinal pigment epithelial (RPE) cells December 2022 Dr Brenda Williams Transplantation of RPE cell sheet under the retina Topic title: Stem Cells Age-related macular degeneration Organogenesis from iPS and ES cells Cortical tissue Eiraku (2008) Cell Stem Cell December 2022 Intestinal crypts Sato (2009) Nature Stratified retinal epithelium Anterior pituitary Nakano (2012) Cell Stem Cell Suga (2011) Nature Dr Brenda Williams Topic title: Stem Cells Thyroid tissue Antonica (2012) Nature Beating cardiomyocytes Zwi-Dantsis (2012) EHJ 28 Thank you If you have any question, please contact me: [email protected]