Clinical cancer II notes stem cell review notes

Stem cells: evolution, function, features Stem cells must sustain species o And are like algae or hydra, or like a protoplast of plants Complex multi-cellular organisms the C values are very close together, differnce being only 4 Embryonic stem cells- the start of life, generate all tissues and organs Adult stem cells are quiescent and replenish a tissue after injury

Environmental control of SC plasticity

Bjornson et al Science 1999 Geiger et al cell 1998 Gussoni et al nature 1999

Stem cell quiescence: low oxygen niche

Mohyeldinet al. Cell Stem Cell 7 (2010)

Human ESCs differentiate spontaneously when cultured under 21% oxygen, significantly reduced under 3% or 5% O2
Ezashiet al. PNAS 102 (2005)

 Stem cell activation: oxidative stress

o Belle et al. Cell Stem Cell 8, 5971, 2011 How to bypass the quiescence? how to become activated?

Cell-density-dependent regulation of neural precursor cell function

o Limoli et al. PNAS 2004;101(45) o Cell growth depends on ROS levels

Stem cell genome integrity

The purpose of quiescence is to protect the genomes

Cytoprotective properties : ABC transporter activity o ABCG2 main stem cell version Noncycling, quiescent posture ,minimizing the change of replication error, low metabolic activity and ROS Loss of Tp53 and expression of BCL2 provies relative protection of cell death resoonses accumulate mutations DNA repair nonhomologous end-joining NHEJ in quiescent cells. Long term deletious effects and genome damage

HSC to DNA damage: either limit DNA damage accrual or effectively respond
Andrew et al cell 142, 2010

Mohrin et al and milyavsky et al and seita et al cell stem cell 2010

Induced Pluripotent Stem Cells (iPSCs)revert adult cells to an embryonic state Somatic cell nuclear transfer into ooplasm Transcription-factor-based reprogramming somatic cells POU5f1, SOX2, KLF4 and MYC POU5F!, SOX2, NANOG, LIN28 Demethylation occurs immediately in somatic cell nuclear transfer, but days to weeks in transcription

Epigenetic memory of iPSCs

Kim et al. Nature. 2010;467

Adult stem cells and cancer stem cells

Leukemia CSCs vs normal HSC

(Bonnet and Dick, Nat Med 1997).

Stem cell and aging

Beerman et al current opinion in immunology 2010

Clinical application of stem cells and cautions iPSCs mesenchymal stem cells (MSC) homing to deliver anti-cancer agent Teratomas brain tumor microenvironment turn MSC into blood vessels NANOG in humans and Mice , serves opposite roles Also note there is a homing effect of stem cells, brain type stem cells in blood will home to the brain

Difference:
Differentiation vs transition/transformation

Quiescence vs proliferation control Embryonic gene expressions