what are stem cells
A stem cell is an unspecialized cell from the embryo, fetus, or adult that:
- under certain conditions, has self–renewal capability by reproducing itself for long periods
(throughout the life of the organism in adult stem cells)
- can differentiate: unspecialized cells give rise to specialized cells that make up the tissues and organs of the body.
- large nuclear to cytoplasmic ratio.
- Thus, stem cells can
a) replenish their own population
b) generate cells that travel down various differentiation / developmental pathways
unique features of all stem cells
- unspecialised
- stem cell does not have any tissue-specific structures that allow it to perform specialized functions.
- However, unspecialized stem cells can give rise to specialized cells during specialization / differentiation. - stem cells are capable of dividing and renewing themselves for long periods
- stem cells may replicate many times.
- When cells replicate themselves many times over, it is called proliferation
- A starting population of stem cells proliferates for many months: If the resulting cells continue to be
unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal by mitotic divisions. - stem cells can give rise to specialised cells
- differentiation: when unspecialised stem cells give rise to specialised cells
- signals inside and outside cells trigger stem cell differentiation
a) Internal Signals:
- During differentiation, differential gene expression occurs when certain genes become activated and other genes become inactivated in an intricately regulated fashion -> differentiated cell develops specific structures, performs certain functions.
- directed differentiation: in the laboratory, a stem cell can be manipulated to become specialized or partially specialized cell types
b) External Signals:
External signals for cell differentiation include
i. chemicals secreted by other cells,
ii. physical contact with neighbouring cells, and
iii. certain molecules in the microenvironment
what is stem cell potency
- range of cell types to which a stem cell can give rise to. (differential potential)
- determined by the number of possible pathways that it can take in its subsequent development, through specialization or differentiation.
- totipotency
- pluripotency
- multipotency
totipotent stem cells
location: formed immediately upon fertilisation, up to 5 days after fertilisation
e.g.: zygotic stem cells
- called the MASTER CELLS of the body as they have the ability to give rise to all cell types that make up an organism.
- They consist only of zygotic stem cells.
- They exist as the fertilized egg (zygote) and the first few cells produced when the zygote divides rapidly by mitosis to form a compact ball of cells called morula
- The zygote marks the earliest stage of totipotency i.e. a single totipotent cell.
- in mammals, such cells have the potential to differentiate into any cell type in the adult body AND any cell of the extra-embryonic membranes (e.g. placenta).
- They have the ability to differentiate into any cell type to form whole organisms.
- Hence totipotent stem cells occur at the earliest stage of embryonic development; before the blastocyst stage.
- These totipotent cells have the potential to develop into a fetus when they are placed into the uterus via in-vitro fertilization (IVF) technique.
pluripotent stem cells
location: formed 5-7 days after fertilisation
eg: embryonic stem cells (ESC)
- These cells descend from totipotent stem cells.
- They have the ability to give rise to types of cells that develop from the three germ layers (mesoderm, endoderm, and ectoderm) from which all the cells of the body arise.
- do not have the potential to make differentiated cells that form the extra-embryonic membranes (e.g. placenta).
- Embryonic Stem Cells (ESCs) are examples for pluripotent stem cells.
- source of human pluripotent stem cells: isolated and cultured from inner cell mass of early human embryos and from fetal tissue that was destined to be part of the gonads.
multipotent stem cells
source: formed after 7 days upon fertilisation
e.g.: adult stem cells
- descend from pluripotent stem cells and can differentiate into many cell lines within a specific type of tissue.
- can only differentiate into a limited number of cell types.
- more specialized than totipotent and pluripotent stem cells.
- Multipotent stem cells are found in adult animals; most organs in the body (e.g., brain, liver) contain them where they can replace dead or damaged cells.
- these adult stem cells may also be the cells that upon accumulation of sufficient mutations, can produce a clone of cancer cells.
stem cells and commitment
- pluripotent stem cels are derived from inner cell mass of the blastocyst
- as they give rise to more pluripotent stem cells, can also generate committed stem cells -> form immediate progenitor cell -> giving rise to smaller population of cells
- progenitor cells can divide a number of times, have limited capacity for self renewal, but with each successive differentiation, cells become progressively mroe differentiated
committed stem cells
committed stem cells: those that have a more limited pathway of development compared to pluripotent cells and are destined to produce a specific group of cells.
- committed stem cells can give rise to more specifically committed stem cells OR generate progenitor cells (precursor cells)
progenitor cells
- Progenitor/precursor cells in fetal or adult tissues: partly differentiated cells that divide and give rise to differentiated cells
- Such cells are “committed” to differentiating along a particular cellular development pathway
A precursor / progenitor cell:
- usually shows some evidence of differentiation, although the process is not complete until the fully differentiated cell has been formed.
- is committed to a limited number of pathways of differentiation / development.
- is more limited in developmental pathways than a multipotent stem cell.
- determine the differentiation of the cell lineage into a particular cell type / group of cell types
significance of having commitment in stem cells
mitotic division of stem cells:
(1) preserves a population of undifferentiated cells while
(2) steadily producing a stream of differentiating cells
Although some types of precursor cells can divide symmetrically to form more of themselves, they do so only for limited periods of time.
embryonic stem cells vs adult stem cells
PAGE 13 TABLE COMPARISON
examples of normal functions of stem cells in living organism: embryonic stem cell
ESC derived from embryos
three categories of embryonic stem cells
1. embryonic stem cells:
- isolated from the inner cell mass (ICM) of the
blastocyst — the stage of embryonic development when implantation occurs.
- ESCs are extracted from frozen surplus 2-5 day
pre-implantation embryos fertilised in vitro
- embryonic germ cells
- isolated from precursor to gonads in aborted fetuses - embryonic carcinoma cells
(FYI)
properties of embryonic stem cell
- Capable of undergoing an unlimited number of symmetrical divisions without differentiating (long-term self-renewal)
- Exhibit and maintain a stable, diploid, normal complement of chromosomes (karyotype)
- Pluripotent ESCs can give rise to differentiated cell types that are derived from all three primary germ layers of the embryo (endoderm, mesoderm, and ectoderm).
- Capable of developing into all fetal tissues during development.
- Clonogenic i.e. a single ESC can give rise to a colony of genetically identical cells, or clones, which have the same properties as the original cell
- easy to obtain pure and can be cultivated in large numbers.
fates of embryonic stem cells in developing embryo
- formation of ICM is the first event that distinguishes cells from one another in terms of their relative positions other than inside or outside of morula
- in icm:
a) layer nearest amniotic cavity: ectoderm
b) layer closest to blastocyst cavity: endoderm
c) mesoderm is in the middle of ectoderm and endoderm - three layered structure called the primordial embryo / gastrula
characteristics of adult stem cells
- An adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ
- can undergo cell division to renew itself, and can differentiate and mature to yield the major specialized cell types of the tissue or organ
- Adult stem cells are rare and are dispersed in tissues throughout the mature animal
- many different types of stem cell, each restricted in the types of specialized cell it can give rise to
- At any time, stem cell numbers in the body are very low making these cells extremely difficult to identify and purify.
- many stem cell types do not grow well in culture, lose their distinctive cellular properties.
primary roles of adult stem cells (somatic stem cell):
- maintain and repair the tissue in which they are found
- replace cells that die because of injury or disease
defining properties of an adult stem cell
Adult stem cells, like all stem cells, share the following characteristics:
- They can make identical copies of themselves for long periods of time (long-term self-renewal)
- able to give rise to fully differentiated cells that have mature phenotypes, are fully integrated into the tissue, and are capable of specialized functions that are appropriate for the
tissue.
- They are clonogenic i.e. a single adult stem cell can give rise to a colony of genetically identical
cells, which then gives rise to all the appropriate, differentiated cell types of the tissue in which it
resides
location of adult stem cells in human body
- very small number of adult stem cells in each tissue
they reside in a specific area of each tissue, remaining quiescent (non-dividing) for many years till thye are activated by cisease or tissue injury - e.g. blood, bone marrow, blood vessels, skin, liver, skeletal muscle
blood stem cells aka hematopoietic stem cells (HSC)
blood cells
1. RBC (erythrocytes): transport oxygen
2. WBC (leukocyte): defense and immunity
3. platelets: fragments of cells involved in blood clotting process
hematopoiesis: process of producing new blood cells, studied extensively because:
- blood cells at all stages are relatively accessible
- blood cells can be grown in culture
- in hematopoiesis, we consider differentiation of multipotent stem cell
- HSC role is to replace blood cells, all blood cells in adult human originate from population of multipotent HSC located in bone marrow (means erythrocytes, leukocytes, platelete all develop from hematopoietic stem cells in bone marrow)
- stem cells are self renewing and precursors of progenitor cells that are committed to one of the hematopoietic lineages at a later stage.
- HSC derived rom the mesoderm in embryo
lineages of hematopoietic stem cells
- early commitment to either myeloid or lymphoid lineage from common myeloid progenitor cell to common lymphoid progenitor cell, then later commitment to the individual lineages leading to fully differentiated celll types
(erythroid and myeloid lineages are from myeloid progenitor cell) - stem cell proliferation is regulated by external signals that are provided by the stromal cells in the form of hematopoietic growth factors and other cytokines
- lymphoid lineage
- produces white blood cells, lymphocytes
include the two antigen specific cell types of the immune system, B and T lymphocytes
B vs T lymphocytes
a) source
B: white blood cells that develop from bone marrow
T: develop in the thymus from precursors that originate from the multipotent stem cells in the
bone marrow and migrate from the bloodstream into the thymus
b) mode of action
B: As part of the immune system, B lymphocytes (B cells) make antibodies and help fight infections.
T: White blood cells that attack virus-infected cells, foreign cells, and cancer cells. T lymphocytes also produce a number of substances that regulate the immune response. Also called T cells.
c) differentiation
B and T: both undergo terminal differentiation after encountering antigens
- myeloid lineage
- Gives rise to the rest of the white blood cells which all derive from the bone marrow in adults.
- leukocytes are mobile units of the body’s immune system. They function as:
a) defence against pathogen invasion by phagocytosis,
b) identification and destruction of cancer cells that arise within the body,
c) the “clean-up crew” to remove / phagocytize debris from dead / injured cells during wound healing / tissue repair - erythroic lineage
- Yields the red blood cells, or erythrocytes; and the megakaryocytes, which give rise to blood platelets.
- Erythrocytes function mainly to transport gases (oxygen and carbon dioxide) in the blood.
- Blood platelets are for blood clotting functions.
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Carbohydrates28
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Proteins48
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Enzymes30
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Lipids25
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Cell Structure27
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DNA Structure and replication38
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Eukaryotic gene expression49
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Organisation of Eukaryotic genome31
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control of eukaryotic gene expression17
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Gene and Chromosomal Mutations28
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cancer32
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Genetics of Virus26
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Cell signalling24
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Cell membrane33
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Cell and nuclear division46
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stem cells19
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energetics 1: photosynthesis39
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energetics 2: cellular respiration19
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Inheritance40
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Bacteria23
