SUBJECT

Title

Stem Cell Biology

Type of instruction

lecture

Level

master

Faculty

Faculty of Science

Part of degree program

Biology MSc

Credits

Recommended in

Semesters 1-4

Typically offered in

Autumn/Spring semester

Course description

1. Introduction: stem cell biology Different types of stem cells. Totipotent, pluripotent and multipotent stem cells. Stem cells and committed progenitor cells. Self renewal and differentiation in the stem cell repertoire.

2. Embryonic stem cells Embryonic carcinoma (EC) cells. Isolation, characterization and maintenance of murine and human ES cells. Primordial germ cells. Molecular regulators of pluripotency (Oct-4, Nanog, Sox-2, LIF…).

3. Tissue stem cells The origin, development and aging of tissue stem cells. Function of telomerase enzyme. Regulation of asymmetric cell divisions. Origin of cell developmental lineages.

4. The Notch signaling pathway Notch receptors and ligands. Notch signaling - key players and mechanism. Notch signaling in development and disease.

5. Developmental origin of the lympho-hematopoietic system Primitive and definitive hematopoiesis. Hematopoietic cell lineages. Assays for hematopoietic stem and progenitor cells – cell surface markers, in vitro cultures, analysis in repopulated hosts.

6. Mesenchymal stem cells Origin, development and differentiation of mesenchymal stem cells. Differentiation into osteoblasts, chondrocytes and adipocytes. Mesenchymal stem cells in immunoregulation – immunosuppression.

7. The environment surrounding the tissue stem cells – the stem cell niche The structure and properties of stem cell niches. Drosophila ovariole. The epithelial stem cell niche. The hematopoietic stem cells and their microenvironment - endosteal and perivascular niches. Key molecular mechanisms in the maintenance of hematopoietic stem cell niches.

8. Morphogens Morphogen families - Wnt, Hedgehog, BMP/TGF-beta, EGF/FGF. Morphogen signaling. Morphogen gradients. The role of morphogens in stem cell biology.

9. Tissue stem cell plasticity – transdifferentiation Crossing germ layer boundaries. Hematopoietic system from neural stem cells; heart muscle, pancreas and hepatocytes from hematopoietic stem cells? Reproducibility of experimental data? Mechanisms and limitations of stem cell plasticity.

10. Stem cell genomic Gene expression profiling – genetic fingerprints of the stem cells. Genetic promiscuity and master transcription factors. MicroRNA expression and function in stem cells. MicroRNAs as regulators of master transcription factor's and stem cell commitment.

11. Cancer stem cells Tumor heterogeneity, stem cell renewal in carcinogenesis. Inflammation and aging. Leukaemias, lymphomas and solid tumors. The stem cell origin of cancer?

12. Stem cell derived – non-malignant – diseases Feto-maternal microchimerism. Hematopoietic stem cells and autoimmune diseases. Pulmonary, liver and kidney fibrosis. Atherosclerosis.

13. Bone marrow transplantation. Autologous and allogeneic transplantation. Conditioning regimens. The stem cell graft – bone marrow, mobilized peripheral blood, umbilical cord blood. Hematopoietic and immune reconstitution after BMT. Graft versus host diseases (GVHD) and graft versus tumor (GVT) effect.

14. Regenerative medicine Tissue/organ regeneration in animals. Stem cells for tissue repair – hypes and hopes. Stem cell therapy for diabetes, heart infarct, and Parkinson's disease? Stem cell based tissue engineering.

Readings

Lecture notes on CD (Ferenc Uher)
Stewart Sell (ed): Stem Cells Handbook, Humana Press, Totowa, 2004