Foty - Stem Cells Flashcards
Cell Intrinsic Regulation
Sox2-Oct4-Nanog - negative transcription factors, repress differentiation genes
Ronin: DNA binding protein that also represses
Cell Extrinsic Pathway
LIF (leukimia inhibitory factor) and BMP use JAK-STAT3 pathway and SMAD-ID pathway (respectively) to block MAPK pathway, preventing environment from causing differentiation
Stem Cell Niche
Microenvironment within which stem cells live undifferentiated (chemical, physical, molecular..)
ex: Intestinal crypt niche, stem cells differentiate to TA & Paneth, paneth remains in niche with stem while TA go out to become new cells; can’t divide without paneth present
Stem Cell properties
Undifferentiated, self-renewal.
Symmetric Division: under stress, need to form a ton of stem cells
Assymetric division: Normal, when stem cell forms differentiated and new stem cell
Types of Stem Cells (3)
1) Adult Stem Cell (germline)
2) Embryonic Stem Cell (embryo)
3) Cancer Stem Cells (drive tumorigenesis)
De-Differentiation
i.e. induced pluripotency, make stem cell from differentiated cell by working backwards
Gold Standard for Stem Cell sorting?
FACS Fluorescence-activated cell sorting (uses fluorescent flow cytometry to separate stem cells based on tagged surface markers)
Maintenance of Differentiation (4)
All + Feedback:
1) transcription factors activated by differentiation bind their own enhancer (+ feedback)
2) synthesize proteins that affect chromatin to keep gene accessible
3) cell makes more of differentiating signal molecule and receptor
4) neighboring cells stimulate each other to remain differentiated
Induced Pluripotent Stem Cell key genes (SOCK)
Oct4, Sox2, Klf4, cMyc
Cancer Stem Cells
Unlike previously thought, cancer develops from cancer stem cells (CSCs). If chemo targets tumor but ignores stem cells (since they proliferate slower, have multidrug resistance, etc.), tumor will return. New cancer therapies aim to target CSCs