Stem Cells Flashcards
What properties define stem cells?
- ) They are unspecialized
2. ) The can be induced to differentiate into specific cells
Are unspecialized and can self renew
Stem Cells
Can be induced to differentiate into cells with special functions
Stem cells
Predominates under steady-state conditions and serves to maintain a balance between differentiated and undifferentiated cells
Asymmetric division
Predominate when stem cells must expand in number
-Ex: during development or injury
Symmetric divisions
Asymmetrical segregation of factors that promote “stemness” to one daughter cell and not the other
Asymmetric division
What essentially happens during asymmetric division?
2 cells are formed, one cell differentiates and and the other remains undifferentiated
What are the two ways to regulate stem cell self-renewal
- ) Cell intrinsic regulation
2. ) Cell extrinsic regulation
What are three transcription factors of cell-intrinsic regulation of stem cell self-renewal?
Sox2, Oct4, and Nanog
Negatively regulate expression of differentiation-promoting genes
Sox2, Oct4, and Nanog
Suppresses transcription of differentiation-inducing genes such as GATA4 and GATA6
-intrinsic regulator
Ronin (DNA binding protein)
In the cell extrinsic pathway, LIF and BMP work through STAT3 and SMAD-Id to block the
MAPK pathway
Blocking differentiation in stem cells leads to
Self renewal
Describes the microenvironment in which the stem cells reside in their undifferentiated state
Stem cell Niche
Tissue injury results in a respecification of the
Niche environment
Respecification of the niche environment can result in increased
Proliferation and differentiation
Stem cell division with maintenance of the undifferentiated state
Stem cell self-renewal
An example of a stem cell niche is the
Intestinal crypt
Stem cells in the intestinal crypt can give rise to
TA cells and Paneth cells
Remain close in proximity to stem cells
-1:1 ratio with intestinal stem cells and stem cells won’t divide without them
Paneth cells
What are the three types of stem cells
- ) Adult stem cells
- ) Embryonic stem cells
- ) Cancer stem cells
An undifferentiated cell found in a differentiated tissue that can self renew and differentiate into all of the specialized cell types of the tissue from which it originated
Adult stem cell
A type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing forced expression of specific genes
Induced pluripotent stem cells (iPS cells)
Undifferentiated cells derived from a 5-day preimplantation embryo
-can differentiate into a wide variety of specialized cell types
Embryonic stem cells
Cells that drive tumorigenesis and also give rise to differentiated progeny
Cancer stem cells (CSC)
A cell that through the process of differentiation has acquired a specialized structure and function
Differentiated cell
A cancer in which the cells are mature and look like cells in the tissue from which it arose
Differentiated cancer cell
A cell that has not yet acquired a special structure or function
Undifferentiated cell
A cancer in which the cells are very immature and “primitive” and do not look like cells from which it arose
Undifferentiated Cancer cell
A process by which a partially or terminally differentiated cell reverts to an earlier developmental stage
Dedifferentiation
The potential to differentiate is termed
Potency
Can give rise to embryonic and extraembryonic tissues
-Exist up until 8 cell embryo
Totipotent stem cells
Descendants of totipotent stem cells that can differentiate into cells from any of the three germ layers
Pluripotent stem cells
An example of pluripotent stem cells are
ICM cells
Stem sells that can differentiate into a number of cells, but only those of a closely related family of cells
-ex: hematopoetic stem cell
Miltipotent stem cells
Stem cells that can differentiate into only a few cells, such as lymphoid or myeloid stem cells
Oligopotent stem cells
When stem cells can produce only one cell type, their own, they are termed
-ex: muscle stem cells
Unipotent stem
Unipotent stem cells are distinguished from non-stem cells because they have the property of
Self-renewal
Their primary role is to maintain and repair the tissue in which they are found
Adult stem cells
In bone marrow, two populations of adult stem cells have been identified. What are they?
- ) Hematopoetic stem cells
2. ) Stromal stem cells
Forms all of the types of blood cells in the body
Hematopoetic stem cells
Form bone, cartilage, fat, and connective tissue
Stromal stem cells
Obtained from the inner cell mass of 4-5 day old blastocysts
Embryonic stem cells
Can be cultured in vitro so that they are either prevented from differentiating or they are forced to differentiate
Embryonic Stem Cells
In order to culture ES cells, ICM cells are plated onto a layer of
-provide source of growth and attachment
Mouse fibroblast feeder cells
To culture ES stem cells in vitro and prevent them from differentiating, ICM cells are plated with factors that inhibit differentiation such as
Leukemia inhibitory factor (LIF)
LIF binds to a heterodimer composed of LIF receptor and gp130, which activates
JAK/Stat3 signalling
The activation of JAK/Stat3 signaling effectively blockes the
MAPK pathway (and thus differentiation)
Typically, hematopoetic stem cells (HSCs) from long bones, hips, and spine are isolated using a method called
Multi-parameter flow cytometry
We can identify stem cells using cell surface markers directed against specific
Membrane receptors
The most common method of isolating stem cells is
Fluorescence-activated cell sorting (FACS)
How are adult and embryonic stem cells stimulated to differentiate in vitro?
- ) Change chemical composition of medium
- ) Alter surface of culture dish
- ) Introduction of certain genes
Gene expression must be maintained for a differentiated cell to remain committed to a specific
Phenotype
To maintain gene expression, the transcription factor whose gene is activated can bind the
Enhancer of its own gene
To maintain gene expression, we synthesize proteins that act on chromatin to keep the gene
Accessible
If differentiation is dependent on a particular signaling molecule, the cell can make both the molecule and its receptor to maintain
Gene expression
Cells can interact with one another to stimulate eachother to remain
Differentiated
What are the five ways of obtaining human pluripotent stem cells?
- ) from Morula (before 16 cells)
- ) from ICM of blastocyst
- ) from primordial germ cells of a fetus
- ) from adult
- ) through somatic nuclear transfer
There are 24 candidate genes for pluripotency factors that can be used to make iPS cells, what are 4?
- ) Oct4
- ) Sox2
- ) Klf4
- ) cMyc
One of the challenges to reprogramming is that we have to perform genomic insertion and inserted genes can insert
Mutations
Creates the potential for tumors because it is an oncogene
cMyc
Formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of disease
StemBANCC
A “human liver” was synthesized using which stem cells?
Hepatocytes, endothelial stem cells, and mesenchymal stem cells
In medical research, iPS cells have been used for
Disease modeling and drug development, organ synthesis, and tissue repair
Tumors arise from cells termed cancer stem cells that have properties of normal stem cells, particularly
Self-renewal and Multipotency
Unregulated cell growth is due to a disruption in the regulatory mechanism in
Stem cell renewal
A stem cell disorder, and not a simple mechanism whereby cell proliferation is disrupted
Cancer
One problem with cancer treatment is that stem cells divide slowly, giving themselves plenty of time to repair any damage caused by
Radio- or chemotherapy
Stem cells retain the essential property of self-protection through the activity of
Multiple drug resistance transporters
Thus, a mutation that allows for unbridled cell growth will render chemotherapy
Ineffective
Conventional chemotherapies kill the bulk of the tumor but do not eliminate the
Cancer stem cells giving rise to it
Tend to be chemoresistant
Stem cells
The most common primary brain tumor with a median survival of about 1 year
Glioblastoma
This poor prognosis is due to therapeutic resistance to
Temozolomide
