Graduate Cell Biology Course · Regenerative Medicine Track
Stem Cells — Biology, Reprogramming & Regenerative Medicine
From the inner cell mass to Yamanaka reprogramming to clinical organoids — the biology of cells that can make any other cell, and the medical revolution they have launched.
About This Course
A stem cell is defined by two properties: it can self-renew(divide to produce another stem cell) and it can differentiate(produce at least one specialised cell type). Every cell in your body traces its lineage back, through a small number of divisions, to a stem cell. The cells in your gut epithelium turn over every 3–5 days; the cells in your blood every ~120 days; the cells in your skin every ~30 days. A human body is, physically, a continuous reconstruction from stem-cell reservoirs.
Ten modules trace the field from the foundational Till-McCulloch experiments of the 1960s, through the derivation of embryonic stem cells (Evans 1981, Thomson 1998), through the revolutionary 2006 Yamanaka reprogramming that won a Nobel six years later, through the adult-stem-cell niches of skin, blood, gut, and brain, through the cancer-stem-cell hypothesis, and finally into the clinical frontier of organoids and iPSC-derived cell therapies now in Phase-2/3 trials for AMD, Parkinson’s, diabetes, and spinal-cord injury.
This is the cell biology on which a large fraction of 21st-century medicine will be built.
Featured Lecture — Cédric Blanpain (ULB)
Cédric Blanpain (ULB Brussels, HHMI) is one of the founders of modern skin-stem-cell biology — his group showed that the committed-progenitor model, not the hierarchical stem-cell model, best describes interfollicular epidermis turnover. His iBiology lecture on Skin Stem Cells: Biology and Promise for Regenerative Medicine is the canonical introduction to the adult stem cell populations that anchor Module 4 and, by extension, the whole adult half of the course.
Key Concepts
Till-McCulloch CFU-S (1961)
Colony-forming unit assay; first quantitative stem-cell evidence.
Yamanaka Factors (2006)
Oct4 + Sox2 + Klf4 + c-Myc reprograms fibroblast to iPSC.
Schofield Niche (1978)
Stem-cell identity requires a specific microenvironment.
Potency Hierarchy
Totipotent > Pluripotent > Multipotent > Unipotent.
Core Pluripotency Circuit
Oct4 + Sox2 + Nanog co-bind and co-regulate.
Waddington Landscape
Development as trajectory on an epigenetic landscape.
Ten Modules
M0
What Is a Stem Cell?
Self-renewal and differentiation, potency hierarchy (toti/pluri/multi/unipotent), Till & McCulloch 1961 clonogenic assay, stochastic vs deterministic fate.
M1
Embryonic & Pluripotency
ICM to ESC derivation (Evans 1981, Thomson 1998), Oct4/Sox2/Nanog core circuit, naive vs primed pluripotency, teratoma assay.
M2
iPSC & Yamanaka Reprogramming
Yamanaka 2006 four factors, stochastic vs deterministic reprogramming, barriers (senescence, epigenetic), modern chemical/mRNA reprogramming.
M3
Adult Stem Cells & Niches
Schofield 1978 niche concept, WNT/Notch/BMP signalling, asymmetric vs symmetric division, label-retaining cells, clonal dynamics.
M4
Skin & Epithelial Stem Cells
Interfollicular basal stem cells, hair-follicle bulge, Lgr5+ cells, committed progenitor model (Blanpain lab). Embedded lecture.
M5
Haematopoietic Stem Cells
Weissman HSC purification, long-term vs short-term repopulation, bone marrow transplantation (the first stem-cell therapy, Thomas 1990 Nobel), CAR-T.
M6
Neural Stem Cells
Adult neurogenesis (SVZ, SGZ hippocampus), Altman 1962 controversy, Alvarez-Buylla, human adult neurogenesis debate (Sorrells 2018 vs Moreno-Jimenez 2019).
M7
Cancer Stem Cells
Bonnet & Dick 1997 AML CSCs, clonal evolution vs CSC model, plasticity, drug resistance, targeting CSCs therapeutically.
M8
Organoids & Regenerative Medicine
Lgr5+ intestinal organoids (Clevers 2009), cerebral organoids (Lancaster), RPE for AMD, cardiac patches, iPSC-derived cell therapies.
M9
Ethics & Clinical Trials
14-day rule, iPSC ethical workarounds, current clinical trials (RPE, Parkinson, spinal cord), mitochondrial replacement, stem-cell tourism.
Cross-Links
Cell Physiology,Molecular Biology,Organelles,Mitochondria,Disease & New Approaches,Omics,Bioinformatics,Neuroscience.
Foundational References
- [1] Till, J. E. & McCulloch, E. A. (1961). A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res., 14, 213–222.
- [2] Evans, M. J. & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292, 154–156.
- [3] Thomson, J. A. et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.
- [4] Takahashi, K. & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.
- [5] Schofield, R. (1978). The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells, 4, 7–25.
- [6] Bonnet, D. & Dick, J. E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med., 3, 730–737.
- [7] Sato, T. et al. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 459, 262–265.
- [8] Blanpain, C. & Fuchs, E. (2014). Plasticity of epithelial stem cells in tissue regeneration. Science, 344, 1242281.