Foty - Cell differentiation Flashcards
totipotent
pluripotent
t - Stem cells that are produced from the fusion of an egg and sperm as well as from the first few divisions. Such cells can give rise to embryonic and extra-embryonic tissues.
p - descendants of totipotent cells. Not as great as totipotent cells but still awesome. Can differentiate into cells from any of the three germ layers. Inner Cell Mass (ICM) cells are pluripotent
Multipotent
Oligopotent
Unipotent
M - can differentiate into a number of cells but only those closely related family of cells. Ex=hematopoietic stem cells
O - stem cells that can differentiate into only a few cells such as lymphoid or myeloid stem cells
U - cells can only produce only one cell type, their own, but they have the property of self-renewal which distinguishes them from non stem-cells. Ex=muscle cells
How are stem cells cultured in vitro?
- Either using mouse feeder cells
- Or using LIF which essentially inhibits the proliferation of these stem cells.
Regulation of stem cell self-renewal
intrincis and extrinsic
- cell-intrinsic regulation - Sox2-Oct4-Nanog are transcription factors that negatively regulate expression of differentiation-promoting genes. Also, DNA binding protein Ronin suppresses transcription of differentiation-inducing genes such as GATA4 and GATA6.
- Cell-extrinsic regulation - LIF, BMP work through STAT3 and SMAD-Id to block MAPK pathway
asymmetric vs symmetric
A - stem cell turns into other cell
S - stem cell multiplies into more stem cells. Happens during injury.
Cell intrinsic regulation
Sox2, Oct4, and Nanog negativelyl regulate expression of differentiation-promoting genes. Keep differentiating genes down.
Ronin suppresses transcription of differentiation-inducing genes. Keep differentiating genes down.
cell-extrinsic regulation
LIF, BMP are examples of extracellular ligands that can cause extrinsic regulation. They work through STAT3 and SMAD-Id to block MAPK pathway. MAPK would cause differentiation. So this pathway keeps differentiation low.
Intestinal crypt niche
example of niche microenvironment. The crypt cells, which are the stem cells, can’t divide without paneth cells.
3 types of stem cells
Adult, embryonic, and cancer
dedifferentiation
partially or terminally differentiated cells revert back to an earlier stage. Holy grail.
What is the gold standard for isolating stem cells?
Fluorescence-activated cell sorting (FACS)
How do cells stay in the differentiated state until they are fully differentiated?
1) The transcription factor whose gene is activated by signal transduction can bind to the enhancer of its own gene (positive feedback)
2) Synthesize proteins that keep chromatin accessible.
3) Cell can make signaling molecule and receptor.
4) Cells can interact with neighboring cell lso that each stimulates the next.
4 candidates for pluripotency factors
Oct4, Sox2, Klf4, cMyc (SOCK)
- These genens are sufficient to turn other cells into pluripotent cells
Cancer stem cells
Basically cancer is a stem cell issue because a mass of proliferation comes from the stem cells. Generally these cancer stem cells are very drug resistant. Current chemos attack the tumor but have difficulty getting the tumor stem cell so it will keep coming back.
Jak/STAT signaling
when Lif binds to a heterodimer it activattes JAK/STAT and effectively blocks the MAPK pathway so the stem cells don’t differentiate