iPSCs are pluripotent; unlike ESC, iPSCs are not derived from the embryo, but instead created from differentiated cells in the lab through a process – cellular reprogramming.

1. INDUCED PLURIPOTENT
STEM CELLS (iPSCs)

2. Background of iPSCs
 Cellular differentiation has long been considered a
permanent process*
 Specialized cell types were described as ‘terminally
differentiated’**
 Shinya Yamanaka et al. (2006) – demonstrated
that differentiated skin cells could be turned back to
a pluripotent embryonic-like state – iPSCs***

3. Background of iPSCs
 iPSCs are pluripotent; unlike ESC, iPSCs are
not derived from the embryo, but instead
created from differentiated cells in the lab
through a process – cellular
reprogramming.

4. Discovery of iPSCs
1. Yamanaka hypothesis
2. Testing of 24 possible pluripotency genes
3. Yamanaka factors: Oct4, Sox2, Klf4, c-Myc
4. Cellular reprogramming

5. How are the Yamanaka
Factors introduced into
cells?

6. Transgenics
 The delivery of a sequence of genetic material
(transgene) into cells growing in a petri dish*
 Retroviral vectors –modified viruses that
deliver foreign genetic material into a cell**

7. How do scientists know that
differentiated cells have been
reprogrammed into iPSCs?

8. Testing for Pluripotency
1. Morphology (cell shape)
2. Genomics (types of genes expressed)
3. Function (ability to differentiate)

9. Morphology
 Change in morphology of the cells*
 Example: skin cells grow as flattened cells in
a dish; however, as they become
reprogrammed, the iPSC grow in round
clumps known as colonies

10. Expression of pluripotency markers
 Pluripotency markers
Genes that are only expressed in pluripotent
stem cells and not in other cell types.
Its expression resembles a molecular signature
that lets scientists know that cells have been
reprogrammed to a pluripotent state.

11. Function
 Ability to differentiate into cell types of the 3
embryonic germ layers both in vitro and in vivo*

12. What are the potential
applications of iPSCs?

13. Tool to study human diseases
 IPS cells are powerful method for creating
patient- and disease-specific cell lines for
research.
 IPSCs are useful tools for drug development and
modeling diseases.
 Scientists hope to use them in transplantation
medicine.

14. CANCER

15. What is Cancer?
 Abnormal cells in which the processes regulating
normal cell division are disrupted.
 In cancer, the control systems that prevent cell
overgrowth & invasions are disabled.
 They no longer require signals to induce cell
growth and division.

16. What is Cancer?
 Acquire abnormal functions; develop new
characteristics – change in structure, decreased
cell adhesion & production of new enzymes.

17. Malfunctioning genes
 Proto-oncogenes
Produce proteins that enhance cell division*
 Tumor suppressors
Make proteins that normally prevent cell division or
cause cell death.
 DNA repair genes
Help prevent mutations that lead to cancer.

18. Protein that stimulates cell cycle
Nucleus
Protein kinases
RAS (G protein)
Growth factor
Proto-oncogenes &
Signal transduction (RAS
pathway)
Transcription factor

19. Tumor suppressor genes
 Mutations result in cells that no longer show
normal inhibition of cell growth and division.
 Ex.: APC – mutations lead to FAP

21. DNA repair genes
 Involved in DNA repair and maintenance of
chromosome structure.
 Environmental factors: ionizing radiation, UV light,
chemicals
 Ex.: XP (mutation) – individuals who are sensitive to UV;
thousand-fold increase in incidence of all types of skin cancer
 Bloom syndrome (BLM) – increased risk of cancer, lung
disease, and diabetes.

22. Cyclin-dependent kinases
 Proteins that control timing
of events in cell cycle.
 Kinase – adds phosphate to
various proteins required for
progression of cell cycle.
 Specific CDK at enrty points
to G1,S, & M phases.
 Loss of this regulation is the
hallmark of cancer.
 p53 – stop cell cycle by
inhibiting CDK; mutation can
lead to cancer.

23. NORMAL CELLS CANCER CELLS
Require external growth factors to
divide*
They divide whether or not growth
factors are present**
Show contact inhibition*** Continue to grow after they touch other
cells, forming a large mass to form
The cells age and die, and replaced in
a controlled & orderly manner.
Unlimited number of cell divisions
(activation of telomerase).
Cease to divide and die when there is
DNA damage or when division is
abnormal
Continue to divide, even when there is
a large damage to DNA or when it is
abnormal

24. MYELOMASLYMPHOMALEUKEMIASARCOMASCARCINOMAS
Types of Tumors