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Stem cell differentiation

Terms in this set (45)

What is the definition of stem cell differentiation?
progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and lead tot he formation of specialized cells, tissues, and organs

OR

the process whereby relatively unspecialized cells (ie embryonic or regenerative cells) acquire specialized structural and /or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history
What is a totipotent stem cell?
these cells have unlimited capability and have the ability to form extraembryonic membranes and tissues, the embryo itself, and all postembryonic tissues and organs.

They are produced from the fusion of an egg and sperm cell, and are produced by the first few divisions of the fertilized egg.
What is a pluripotent stem cell?
These cells are capable of of giving rise to most but not al tissues of an organism (can differentiate into any of the cells of the 3 germ layers). An example would be inner mass cells

They derive from totipotent cells
What is a multipotent stem cell?
These cells are committed to give rise to cells that have a specific function. An example is blood stem cells (give rise to platelets, WBCs, RBCs)

Can produce only cells of a closely related family of cells
What type of cells are stem cells?
pluripotent
Where are totipotent cells found in humans?
the zygote and early embryonic cells
What are stem cells?
They are primal cells found in all multi-cellular organisms. They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types.
Name the three locations where stem cells are found in mammals
1. embryonic stem cells- derived from blastocysts
2. adult stem cells- found in adult tissues
3. cord blood stem cells- found in the umbilical cord
What can stem cells in an embryo develop into? What can stem cells in adult organisms develop into?
In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues

In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells
A stem cell has two important properties. What are they?
1. Self renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state
2. unlimited potency: the capacity to differentiate into any mature cell type. In a strict sense, this requires stem cells to be either totipotent or pluripotent.
What is potency?
The differentiation potential (the potential to differentiate into different cell types) of the stem cell.
What is a unipotent cell?
Cells can produce only one cell type but have the property of self-renewal which distinguishes them from non-stem cells
what are embryonic stem cells?
Cells derived from teh epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos

ES cells are PLURIPOTENT and give rise during development to all derivatives of the three primary germ layers:

1. ectoderm
2. endoderm
3. mesoderm

However, they CANNOT contribute to extraembryonic membranes or the placenta
What are adult stem cells?
refers to any cell which is found in a developed organism that has 2 properties:
1. the ability to divide and create another cell like itslef
2. also divide and create a cell more differentiated than itself. Also known as somatic stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults
In what tissues can adult stem cells be found?
brain, bone marrow, peripheral blood, skeletal muscle, skin, and liver
What are hematopoietic stem cells?
They give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, macrophages, and platelets
What are bone marrow stromal cells (aka mesenchymal stem cells)?
give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons
What are neural stem cells?
Give rise to 3 major cell types:
1. astrocytes
2. oligodendrocytes
3. neurons
What are epithelial stem cells?
Found in teh lining of the GI tract and occur in deep crypts; give rise to several cell types:
1. absorptive cells
2. goblet cells
3. paneth cells
4. enteroendocrine cells
Where are skin stem cells found?
the basal layer of the epidermis and at the base of hair follicles

Give rise to :
1. keratinocytes which migrate to the surface and form a protective layer
2. follicular stem cells can give rise to hair folliclesand to the epidermis
Adult stem cells can transdifferentiate in some cases. What cells can transdifferentiate, and into what do they differentiate?
1. Hematopoietic stem cells can differentiate into the 3 major types of brain cells, skeletal muscle cells, cardiac muscle cells, and liver cells
2. bone marrow stromal cells may differentiate into cardiac muscle cells and skeletal muscle cells
3. Brain stem cells can differentiate into : blood cells and skeletal muscle cells
What processes are needed for development of the embryo?
1. cell division
2. cell differentiation
3. pattern formation
4. morphogenesis
5. growth
What are 5 cell behaviors that occur during development?
1. cell to cell communication
2. cell shape changes
3. cell movement
4. cell proliferation
5. cell death (apoptosis)
What are the 4 phases of development to establish germ layers?
1. fertilization
2. cleavage
3. blastulation
4. gastrulation
What is cleavage?
Mitotic divisions without cell growth so in successive cleavages the cells become smaller as the volume remains constant
What is blastulation?
After 12 division cycles, many small cells surrounding a fluid filled cavity (the blastocoel)
What is gastrulation?
Dramatic cell movements, endoderm and mesoderm move to the inside of the embryo, ectoderm on the outside- formation of the basic body plan and establishment of germ layer tissues
Gene regulation allows for cell differentiation. How so?
a cell selectively uses certain genes and synthesizes proteins that are not found in other cell types. The process results in proteins that are the foundation for distinct cell structures, products, and functions
What is combinatorial control of gene expression?
cell development and differentiation rograms are accomplished by "switching" on and off distinct sets of genes. Gene regulatory proteins (transcription factors) that are downstream of signaling cascades bind to control regions of developmentally important genes and suppress or activate their expression
What is the polycomb protein theory?
Polycomb-group proteins is distributed across a special set of
more than 200 developmental genes in human embryonic stem
cells. Polycomb proteins are known to silence gene activity
through chemical, or "epigenetic," modifications that alter the way
that DNA is packaged into chromatin.
It appears that the Polycomb proteins are generally responsible
for maintaining developmental genes in an 'off' state.
What are the 3 transcription factors that are key regulators of the maintenance of a cells pluripotency and self-renewal abilities?
Oct 4, Sox2, nanog

THese 3 factors work together to activate pathwys critical for stem cell identity while repressing those leading to differentiation
What is the bivalent domain theory?
In differentiated cells, chromatin is either 'on' or 'off' in accordance
with the identity of that particular cell--rarely or never in between.
In embryonic stem cells, a totally different structure was found.
The developmental genes of stem cells bear evidence of both
active and repressive states. It's the first time this has been
seen."
The genes appeared to be in a silent state, but with an activating
influence that could allow them to turn on rapidly as needed. The
report suggested that by preserving the potential of key
developmental genes, the bivalent domains may contribute to the
unique ability of embryonic stem cells to form the many different
tissues in the body.
Name 3 ways a cell can gain polarity in development
The point of entry of the sperm cell into the egg may provide
polarity for the cell in some organisms.
In others, mother may deposit mRNAs or proteins in one particular
part of the egg cell.
In yet others, the immediate environment of the egg (e.g., the
uterine lining, or the surface of the soil) may define polarity of the
cell.
In C.elegans, an interaction between mitotic spindle and cell cortex
is responsible for the asymmetria
What is asymmetric cell division?
Cell division producing two daughter cells that exhibit distinct fates

(aka some get more peroxisomes while another gets lysosomes)
What is intrinsic asymmetric cell division?
Intrinsic mechanisms involve the preferential
segregation of cell fate determinants to one of two
daughter cells during mitosis.
Asymmetrically segregated factors that bind cell fate
determinants and orient the mitotic spindle may also
be necessary to ensure the faithful segregation of
determinants into only one daughter cell.
What is extrinsic asymmetric cell division?
Extrinsic mechanisms involve cell-cell
communication.
In metazoans, the social context of a dividing cell provides
positional information and opportunity for cell-cell
interactions.
Interactions between daughter cells or between a daughter
cell and other nearby cells can specify daughter cell fate.
Interaction between a progenitor cell and its environment
can influence cell polarity by directing spindle orientation
and an asymmetric distribution of developmental potential
to daughter cells.
What is a morphogen?
an inducing factor which can invoke more than one response from teh responding tissue
What is induction? What are the 2 types of induceres?
induction: a way to generate complicated patterns from a limited number of signaling molecules

Inducers (chemical signalling molecule) can be soluble (for long range signalling) or one that requires direct physical contact between inducing and responsive tissues
What are the 5 major families of signal proteins that have been identified?
Receptor tyrosine kinase (RTK)
TGF-beta superfamily
Wnt
Hedgehog
Notch
What is the Notch signaling pathway?
(NSP) is a highly conserved pathway for cell-cell
communication.
NSP is involved in the regulation of cellular
differentiation, proliferation, and specification.
Examples, continually renewing adult tissues such as
blood, skin, and gut epithelium not only to maintain stem
cells in a proliferative, pluripotent, and undifferentiated
state but also to direct the cellular progeny to adopt
different developmental cell fates.
In embryonic development to create fine-grained
patterns of differentiated cells,notably during neurogenesis
This process is known as lateral inhibition:
a molecular mechanism whereby individual cells within a
field are stochastically selected to adopt particular cell fates
and the NSP inhibits their direct neighbours from doing the
same.
In addition, the NSP is the basis for vertebrate
segmentation to divide the growing embryo into
regular blocks called somites which eventually form
the vertebrae.
The core of this process relies on regular pulses of
Notch signaling generated from a molecular
oscillator in the presomatic mesoderm.
What are the biomedical applications of stem cell differentiation? Name 3 tissues that can be regenerated
Tissue engineering is a multidisciplinary/ interdisciplinary field
that applies the principles of biology and engineering to develop
tissue substitutes to restore, maintain, or improve the function of
diseased or damaged human tissues
bone substitutes are often required to help repair or replace
damaged or diseased tissues in cases ranging from trauma to
cancer
skin is used in treating patients with diabetic ulcers and burns.
pancreatic beta cells required to produce insulin may be
encapsulated in engineered bimolecular cages that allow them to
function normally in a foreign host without triggering immune
responses
Name some of the applications of stem cell research
understand and prevent birth defects, identify drug targets and test potential therapeutics, toxicity testing, creating tissues for transplantation
What are the 2 ways of producing totipotent cells? Whihc one is more advantageous?
Sexually and asexually

asexual, created by somatic cell transfer, allows for customized therapeutic tissue created from a somatic cell from a patient and a donor that will decrease the risk of rejection
What disease process has many similar characteristics to the development of embryos?
cancer
When do cancer cells migrate?
when they have depleted the resources available to their primary tissues
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