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48 Cards in this Set

  • Front
  • Back
Stem cells are defined strictly based on their
biological potential/functions
what are stem cells
cells regenerate and maintain for a lifetime complete structure/function of adult tissue
stem cell definition based on (3)
self renew
daughter cells commited to differentiation
maintain above 2 for long time (lifetime)
most primitive cells of given lineage=
stem cells
committed/terminally differentiated cells are____descendants of stem cells
clonal
T or F stem cell do not directly contribute to normal tissue FUNCTION
T
*tissue function carried out by terminally diff cells not SC
lineage restriction
as cells differentiate they slowly lose range of differentiation ie become more specific
SC has broadest range of differentiation
-how large is its cell population relative to committed cells
small
SC enter cell cycle_____and divide (quickly or slowly?)
infrequently
slowly
committed cells do cell cycle quickly or slowly?
quickly
committed cells can self-renew/
proliferate, but they are destined to disappear ie enter______
crisis
do SC proliferate
no unless after damage
if have prolif of SC's, ignoring committed cell production, lead to____of terminally differentiated
and result maybe in___formation
decrease
tumor
if all SC's differentiated cause?
eventually we die because differentiated cells not replenished/lost due to crisis and therefore we cannot sustain tissue
input and output within a tissue must be balanced to maintain steadystate homeostasis, during which stem cells should
neither proliferate nor reduce in number
totipotent SC=
make all cell types (even placenta)
only fertilized egg belongs in this category
Pluripotent stem cells
generate all cell types in the body
ex) ESC
Multipotent stem cells
multiple cell types in one cell lineage.
Many stem cells found after birth belong to this group
ex) HSC
Unipotent stem cells
only one type of terminally differentiated
cells
ex) Spermatogonial stem cells
how detect SC based on functional definition
give ex
-look for cells that regenerate and maintain tissues
-ex) spermatogonial transplantation
spermatogonial transplantation
look for SSC activity
transplantation assays for detecting SC's is both qualitative and____
problem with this assay (2)
quantitative (colony#=SC#)
-does not allow us to identify stem cell activity “before” transplantation (its retrospective study) & ignores processes during regeneration
To maintain the steady-state homeostasis (sustaining the structure and function), stem cells should not ____or ____entirely
prolif; differentiate
Uncontrolled proliferation=
Uncontrolled differentiation=
cancer
LOF in tissue
*self renewal does NOT necessarily imply prolif
can also detect SC based on___function
biological
brain has stem cells called
neural SC
NSC location
SVZ
since cannot do brain less recipient how do you detect NSC
-cells from SVZ culture in serum free medium +EGF and/or FGF2
- some cells prolif--> neurospheres
-took cells from neurospheres and cultures, neurospheres reformed
-if culture neuroshpere cells NO GF's then they differentiate
*neurospheres found to have NSC's
summary:
stem cells detected by using __assay
these assays can be done in(2)
they detect stem cells only____
have people seen stem cell under microscope/ purified them
-functional
-in vivo, in vitro
-retrospectively
-no
why study stem cell markers
-functional assays retrospective (not best)
-stem cell markers=molecules made by stem cells therefore can detect stem cells prospectively
how select stem cell using marker
take donor cells
antibody to cell surface antigen
cell seperation
transplant (or functional assay)
*immunological cell sorting
two major ways to isolate marker-expressing cells
immunomagnet cell sorting (MACS)
fluorescent-activated cell sorting (FACS).
problem with marker assays
just because something expresses certain stem cell marker doesn't mean that cell is stem cell ie marker may not be specific to just stem cells
if want to enrich the number of stem cells use___
this expression must correlate with
markers
stem cell activity (measured by functional assay)
mouse HSC express c-Kit and
Thy-1
c-kit expressed by other cell types and Thy1 by
T cells
CD44+CD24- cells are often referred to as
breast cancer stem cells
____is expressed in normal leukocytes and erythrocytes, while ____are expressed in normal B cells and granulocytes
CD44
CD24
to purify SC in future need multiple
positive and negative markers
why use cell surface markers
functional assay need live cells
youd have to kill cell to get molecules inside (can do without killing but very hard)
Stem Cell Niche
ex)
microenvironment surrounding stem cells,
can be involved in regulation of stem cell behavior/fate
fruit fly gonads
fly testis:
GSC bottom of testis on top of ___cells
GSC divide ____to hub-gsc interface
after division one cell attach to hub stays as GSC while other cell gets separted and___
hub
perpendicular
differentiates
if selectively kill individual stem cells in fly testis the remaining GSCs
change direction of cell division to horizontal (not perpendicular)
first fill void space in niche at expense of making committed cell
hub importnqt for gsc niche:
hub oead to cell maintencance by (2)
-secrete Unpaired (Upd--> BMP molecule)-->jak/stat
-cell adhesion
Drosophila GCS asymmetric cell division
involves (3)
growth factors
adherens junction
centrosome
stem cell niche is believed to interact with stem cells and regulate the stem cell ___ decision
fate
invariant asymmetry niche assumed to be a pocket, in this model each stem cell divides asymmetrically to make stem cells and committed cells at ___ratio
1:1
populational asymmetry --> niche is drawn as a
larger tray-like structure
fate decision of individual stem cells can be varied ___or ___
symmetric
asymmetric