Stem Cells (Foty) Flashcards
What 2 properties define stem cells
1) they are unspecialized (undifferentiated) and can self-renew
2) they can be induced to differentiate (into cells with special functions
2 types of self-renewal are
1) asymmetric division
2) symmetric division
Asymmetric division predominates under__________ conditions
It’s purpose is to:
Asymmetric division predominates under steady-state conditions
It serves to maintain a balance between differentiated & undifferentiated cells
There is an asymmetrical segregation of factors that promote “stemless” to one daughter cell & not the others
Aka one cell stays within the “niche” microenvironment & remains undifferentiated while the other is displaced from the niche and differentiates.
Symmetric divisions predominate when _______
When stem cells must expand in number such as during development or after injury
Cell-intrinsic regulation of Stem Cell Self-renewal include _______ transcription factors
These ____regulate expression of differentiation-inducing genes
There is also a DNA binding protein ____ which does what?
Sox2-Oct4-Nanog
NEGATIVELY regulate expression of differentiation-promoting genes
DNA-binding protein Ronin suppresses transcription of differentiation-inducing genes: GATA4 & GATA6
Cell-extrinsic regulation
LIF, BMP work through STAT3, SMAD-Id to block MAPK pathway
The stem cell niche describes_____
What specifies it?
The microenvironment in which stem cells reside in their undifferentiated cells
Cell0cell, cell-substratum interactions, growth factors, cytokines etc specify the niche environment
What results in a re-specification of the niche environment?
Tissue injury –> this can result in increased proliferation & differentiation
Ex: cancer can re-specify the niche; when niche is re-specified, that can give rise to increased proliferation and differentiation
Ex: the intestinal crypt niche
Crypt cells give rise to TA cells that can differentiate into all the cell types (and paneth cells)
Paneth cells remain in close proximity to the stem cells; TA cells move up
Cells won’t divide when they’re by paneth cells
Adult stem cells
Undifferentiated cell found in a differentiated tissue that can self-renew and differentiate into all the specialized cell types of the tissue from which it originated
Primary role: maintain & repair tissue in which they are found
Adult tissues that contain these: Brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, intestinal crypt, liver
Bone marrow: HSCs & Stromal stem cells (form bone, cartilage, fat, connective tissue)
Induced pluripotent stem cells (iPSCs)
Pluripotent stem cells artificially derived from a non-pluripotent cell
Typically an adult somatic cell getting a forced expression of specific genes
Embryonic stem cells
Undifferentiated cells derived from a 5-day preimplantation embryo (blastocyst) that have potential to differentiate into a wide variety of specialized cell types
Can be cultured in vitro under conditions that prevent them from differentiating Or to induce them to differentiate towards a particular phenotype
Cancer stem cells
Cells that drive tumorigenesis and also give rise to differentiated progeny
Dedifferentiation
A process by which a partially or terminally differentiated cell reverts to an earlier developmental stage
Totipotent
Stem cells produced from fusion of egg & sperm/a few divisions
Can give rise to embryonic & extra-embryonic tissues
Pluripotent
Descendants of Totipotent cells that can differentiate into cells from any of 3 germ layers (ectoderm, endoderm, mesoderm)
ICM cells are pluripotent
Multi potent
Stem cells can differentiate into a number of cells but only those of a closely related family of cells
Example: hematopoetic stem cells
Oligopotent
Stem cells can differentiate into only a few cells
Lymphoid or myeloid stem cells
Unipotent
Cells can produce only one cell type, their own, but have the property of self-renewal which distinguishes them from non=stem cells
(Muscle stem cells)
How are stem cells cultured in vitro?
- ICM cells plated onto a layer of mouse fibroblast feeder cells (these are inactivated, they provide a source of growth & attachment )
- ICM cells can be plated onto tissue culture medium containing factors that inhibit differentiation (leukemia inhibitory factor)
- –> LIF binds to a heterodimer composed of LIF receptor & gp130
- –> this activates JAK/Stat3 signaling —>blocks the MAPK pathway to prevent differentiation
How are stem cells identified?
Very rare
-use cell surface markers directed against specific membrane receptors
How are stem cells isolated
Fluorescence-activating cell sorting (FACS)
How are adult and embryonic stem cells stimulated to differentiate
1) changing the chemical composition of the culture medium
2) altering the surface of the culture dish
3) modifying the cells by introducing certain genes
For a cell to remain committed to a particular phenotype what has to be maintained and what are the 4 ways of doing this?
Gene expression has to be maintains
1) Transcription factor whose gene is activated by signal transduction cascade can bind to enhancer of its own gene (positive feedback)
2) synthesizing proteins that act on chromatin to keep gene accessible
3) cell can make both molecule & receptor if differentiation dependent on a particular signaling molecule
4) cells can interact with neighboring cells s.t. Each one stimulates the other to remain differentiated
What is regenerative medicine
Use of stem cells to repair or replace damaged tissues
