Stem Cells Flashcards
Self renewal:
Asymmetric serves to maintain a balance between _____ and ____ cells.
Symmetric divisions predominate when SCs ______, such as _____ or ____.
Self renewal:
Asymmetric serves to maintain a balance between UNDIFFERENTIATED and DIFFERENTIATED cells.
Symmetric divisions predominate when SCs MUST EXPAND IN #, such as DURING TISSUE DEVELOPMENT or AFTER INJURY.
Cell-intrinsic regulation of self-renewal consists of:
____, ____, and ____ TFs which _____ regulate expression of _____-promoting genes
DNA-binding ____ _____ transcription of _____-inducing genes such as ____ and ____.
As long as cells are expressing these factors, they remain as SCs.
Cell-intrinsic regulation of self-renewal consists of:
SOX2, OCT4, and NANOG TFs which NEGATIVELY regulate expression of DIFFERENTIATION-promoting genes
DNA-binding protein RONIN SUPPRESSED transcription of DIFFERENTIATION-inducing genes such as GATA4 and GATA6.
As long as cells are expressing these factors, they remain as SCs.
Cell-extrinsic pathway of SC self-renewal consists of:
___, ___ receptors that work through ____ and ____ to block ___ pathway.
Cell-extrinsic pathway of SC self-renewal consists of:
LIF, BMP receptors that work through STAT3 and SMAD-ID to block MAPK pathway.
Intestinal Crypt Niche:
-SC population are __________, which give rise to _____ cells that differentiate into all the cell types required in the vili and also to ____ cells.
Whereas __ cells move up the flank of the villi, ___ cells remain in close proximity to SCs.
There is a 1:1 ratio between SCs and ___ cells, so without ___ cells, stems won’t divide.
Intestinal Crypt Niche:
-SC population are CRYPT BASE COLUMNAR CELLS, which give rise to TA cells that differentiate into all the cell types required in the vili and also to PANETH cells.
Whereas TA cells move up the flank of the villi, PANETH cells remain in close proximity to SCs.
There is a 1:1 ratio between SCs and PANETH cells, so without PANETH cells, stems won’t divide.
Multipotent SCs can differentiate into a # of cells, but only those of _________. Example: ______
Multipotent SCs can differentiate into a # of cells, but only those of a CLOSELY RELATED FAMILY OF CELLS. Example: HEMATOPOETIC
Oligopotent SCs can differentiate into _______. Examples: _____ or ____
Oligopotent SCs can differentiate into ONLY A FEW CELLS. Examples: LYMPHOID or MYEOLID
Unipotent SCs can produce ______, but have property of _____, which distinguishes them from non SCs
Example: _____
Unipotent SCs can produce ONLY ONE TYPE OF CELL, but have property of SELF-RENEWAL, which distinguishes them from non SCs
Example: MUSCLE SCs
Adult SCs can be found in:
____, _____, ____, _____, ____, ______, and ____.
In bone marrow, there are 2 populations of SCs:
____ and ____
Adult SCs can be found in:
Brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, intestinal crypt, and liver.
In bone marrow, there are 2 populations of SCs:
Hematopoetic and stromal.
How are SCs culture in vitro?
ICM cells are plated onto a layer of ________.
These inactivated cells provide ________ and ______ for ES cells.
OR
Plate ICMs in medium containing factors that _________, such as ____.
___ binds to a heterodimer composed of ____ receptor and ____, which activates ______ signaling, which effectively blocks _____ pathway to prevent ______.
How are SCs culture in vitro?
ICM cells are plated onto a layer of FIBROBLAST FEEDER CELLS.
These inactivated cells provide SOURCE OF ATTACHMENT FACTORS and AND GROWTH FACTORS for ES cells.
OR
Plate ICMs in medium containing factors that INHIBIT DIFFERENTIATION, such as LIF.
LIF binds to a heterodimer composed of LIF receptor and GP130, which activates JAK/STAT signaling, which effectively blocks MAPK pathway to prevent DIFFERENTIATION
Markers commonly used to ID SCs
ESCs:
HSCs:
Mesenchymal SCs:
Neural SCs:
Markers commonly used to ID SCs
ESCs: OCT4, SSEAS
HSCs: CD34, CD133, ABCG2, SCA-1, C-KIT, CD150
Mesenchymal SCs: STRO-1
Neural SCs: NESTIN, PSA-NCAM. P75 NEUROTROPHIN R
How are SCs isolated?
FACS
Methods for maintaining a differentiated state:
- The ____ whose gene is activated by signal transduction cascade can bind to ____ of it’s own gene.
- Synthesizing ____ that act on ____ to keep the gene _____.
- If differentiation is dependent on ______, the cell can make both the ____ and it’s ____.
- Cells can interact with neighboring cells such that each one ______ the other to _________.
Methods for maintaining a differentiated state:
- The TF whose gene is activated by signal transduction cascade can bind to ENHANCER of it’s own gene.
- Synthesizing PROTEINS that act on CHROMATIN to keep the gene ACCESSIBLE.
- If differentiation is dependent on SIGNALING MOLECULE, the cell can make both the MOLECULE and it’s RECEPTOR.
- Cells can interact with neighboring cells such that each one STIMULATES the other to REMAIN DIFFERENTIATED.
To be useful for transplant purposes, SCs must be reproducibly made to:
Proliferate extensively and generate sufficient quantities of cells for making tissue
Differentiate into desired cell types
Survive in recipient after transplant
Integrate into surrounding tissue after transplant
Function appropriately for the duration of pts life
Avoid harming pt
Avoid immune rejection
5 Ways of Obtaining Human PSCs
1) from morula-stage embryo (pre-16 cells)
2) from ICM of blastocyst
3) from primordial germ cells of fetus
4) from adult
5) through somatic cell nuclear transfer
IPSCs start off as ____ cells, and reprogrammed via ____, _____, or _______.
Only 4 TFs need to be transfected in order to cause stemness:
IPSCs start off as ADULT cells, and reprogrammed via NUCLEAR TRANSFER, CELL FUSION, or GENETIC REPROGRAMMING.
Only 4 TFs need to be transfected in order to cause stemness:
OCT4, SOX2, KLF4, CMYC
