Gene Expression in Stem Cells

Gene Expression in Stem Cells
Symmetric division maintains stem cell lines and asymmetric division yields
differentiated cells.
LEARNING OBJECTIVES
Discuss the types of cell division that can occur to add cells during development
KEY TAKEAWAYS
Key Points
 Symmetric cell division of stem cells ensures that a constant pool of stem
cells is available by giving rise to two identical daughter cells both endowed
with stem cell properties.
 Asymmetric division of stem cells results in the production of only one
stem cell and a progenitor cell with limited self-renewal potential.
 Progenitor cells that are produced via asymmetric cell division will go
through additional rounds of cell division until they are terminally
differentiated into a mature, specialized cell.
 Asymmetric division can be controlled by both intrinsic and extrinsic
factors.
 Intrinsic factors involve differing amounts of cell-fate determinants being
distributed into each daughter cell, while extrinsic factors involve
interactions with neighboring cells and the micro and macro environment
of the precursor cell.
Key Terms
 totipotency: the ability of a cell to produce differentiated cells upon

division
 progenitor cell: a biological cell that, like a stem cell, has a tendency to
differentiate into a specific type of cell, but is already more specific than a
stem cell and is pushed to differentiate into its “target” cell.
 autologous: derived from part of the same individual (i.e. from the
recipient rather than the donor)
 morula: a spherical mass of blastomeres that forms following the splitting
of a zygote; it becomes the blastula
 pluripotent: able to develop into more than one mature cell or tissue type,
but not all
Adding cells through cellular division
Stem cells are undifferentiated biological cells found in multicellular organisms,

that can differentiate into specialized cells (asymmetric division) or can divide to
produce more stem cells (symmetric division). In mammals, there are two broad
types of stem cells: embryonic stem cells, which are isolated from the inner cell
mass of blastocysts, and adult stem cells, which are found in various tissues. In
adult organisms, stem cells and progenitor cells act as a repair system for the
body by replenishing adult tissues. In a developing embryo, stem cells can
differentiate into all of the specialized cells (including ectoderm, endoderm and
mesoderm cells) but also maintain the normal turnover of regenerative organs,
such as blood, skin, or intestinal tissues. The pathway that is taken to produced
specialized cells included: the embryonic cells develop from totipotent cells, to
pluripotent cells which undergo differentiation and become more specialized.
The key component however, in the ability to maintain tissues is the ability to
maintain a key of stem cells.
Stem Cells: Pluripotent, embryonic stem cells originate as inner cell mass (ICM)
cells within a blastocyst. These stem cells can become any tissue in the body,
excluding a placenta. Only cells from an earlier stage of the embryo, known as the
morula, are totipotent, able to become all tissues in the body and the
extraembryonic placenta.
There are three accessible sources of autologous adult stem cells in humans: (1)
bone marrow, which requires extraction by harvesting (i.e., drilling into bone);
(2) adipose tissue (lipid cells), which requires extraction by liposuction; and (3)
blood, which requires extraction through apheresis (wherein blood is drawn
from the donor, passed through a machine that extracts the stem cells, and
returned to the donor). Stem cells can also be taken from umbilical cord blood
just after birth. Of all the stem cell types, autologous harvesting involves the least
risk. By definition, autologous cells are obtained from one’s own body, just as one
may bank his or her own blood for elective surgical procedures. Highly plastic
adult stem cells are routinely used in medical therapies, for example in bone
marrow transplantation. Stem cells can now be artificially grown and
differentiated into specialized cell types with characteristics consistent with
muscle or nerve cells through cell culture. Embryonic cell lines and autologous
embryonic stem cells generated through therapeutic cloning have also been
proposed as promising candidates for future therapies.
Symmetric and asymmetric cell division
To ensure self-renewal, stem cells undergo two types of cell division: symmetric
and asymmetric. Symmetric division gives rise to two identical daughter cells
both endowed with stem cell properties. Asymmetric division, on the other hand,
produces only one stem cell and a progenitor cell with limited self-renewal
potential. Progenitors can go through several rounds of cell division themselves
before terminally differentiating into a mature cell.. It is possible that the
molecular distinction between symmetric and asymmetric division lies in
differential segregation of cell membrane proteins between the daughter cells.
An alternative theory is that stem cells remain undifferentiated due to
environmental cues in their particular niche. Stem cells differentiate when they
leave that niche or no longer receive those signals.
Symmetric and Asymmetric Division: This diagram illustrates stem cell

division and differentiation, through the processes of (1) symmetric stem cell
division, (2) asymmetric stem cell division, (3) progenitor division, and (4)
terminal differentiation. Stem cells are indicated by (A), progenitor cells by (B),
and differentiated cells by (C).
An asymmetric cell division produces two daughter cells with different cellular
fates. This is in contrast to normal symmetric cell divisions, which give rise to
daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to
give rise to two distinct daughter cells: one copy of the original stem cell as well
as a second daughter programmed to differentiate into a non-stem cell fate.
In principle, there are two mechanisms by which distinct properties may be

conferred on the daughters of a dividing cell. In one, the daughter cells are
initially equivalent but a difference is induced by signaling between the cells,
from surrounding cells, or from the precursor cell. This mechanism is known as
extrinsic asymmetric cell division. Extrinsic factors involve interactions with
neighboring cells and the micro and macro environment of the precursor cell.
In the second mechanism, the prospective daughter cells are inherently different
at the time of division of the mother cell. Because this latter mechanism does not
depend on interactions of cells with each other or with their environment, it
must rely on intrinsic asymmetry. The term asymmetric cell division usually
refers to such intrinsic asymmetric divisions. Intrinsic factors generally involve
differing amounts of cell-fate determinants being distributed into each daughter
cell.
Animals are made up of a vast number of distinct cell types. During development,
the zygote undergoes many cell divisions that give rise to various cell types,
including embryonic stem cells. Asymmetric divisions of these embryonic cells
gives rise to one cell of the same potency (self-renewal), and another that may be
of the same potency or stimulated to further differentiate into specialized cell
types such as neurons. Asymmetric division of stem cells plays a key role in
development by allowing for the differentiation of a subset of daughter cells
while maintaining stem cell pluripotency. Since it can be controlled by both
intrinsic and extrinsic factors, upon delineating these particular factors it may be
possible to use this knowledge in applications of tissue and whole organ
generation.
Stem cell research offers great promise for understanding basic mechanisms of human
development and differentiation, as well as the hope for new treatments for diseases
such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction.
However, human stem cell (hSC) research also raises sharp ethical and political
controversies. The derivation of pluripotent stem cell lines from oocytes and embryos
is fraught with disputes about the onset of human personhood. The reprogramming of
somatic cells to produce induced pluripotent stem cells avoids the ethical problems
specific to embryonic stem cell research. In any hSC research, however, difficult
dilemmas arise regarding sensitive downstream research, consent to donate materials
for hSC research, early clinical trials of hSC therapies, and oversight of hSC research.
These ethical and policy issues need to be discussed along with scientific challenges
to ensure that stem cell research is carried out in an ethically appropriate manner. This
article provides a critical analysis of these issues and how they are addressed in
current policies.
III. Embryonic Stem Cell Research

Pluripotent stem cell lines can be derived from the inner cell mass of the 5- to 7-d-old
blastocyst. However, human embryonic stem cell (hESC) research is ethically and
politically controversial because it involves the destruction of human embryos. In the
United States, the question of when human life begins has been highly controversial
and closely linked to debates over abortion. It is not disputed that embryos have the
potential to become human beings; if implanted into a woman’s uterus at the
appropriate hormonal phase, an embryo could implant, develop into a fetus, and
become a live-born child.
Some people, however, believe that an embryo is a person with the same moral status
as an adult or a live-born child. As a matter of religious faith and moral conviction,
they believe that “human life begins at conception” and that an embryo is therefore a
person. According to this view, an embryo has interests and rights that must be
respected. From this perspective, taking a blastocyst and removing the inner cell mass
to derive an embryonic stem cell line is tantamount to murder (4).
Many other people have a different view of the moral status of the embryo, for
example that the embryo becomes a person in a moral sense at a later stage of
development than fertilization. Few people, however, believe that the embryo or
blastocyst is just a clump of cells that can be used for research without restriction.
Many hold a middle ground that the early embryo deserves special respect as a
potential human being but that it is acceptable to use it for certain types of research
provided there is good scientific justification, careful oversight, and informed consent
from the woman or couple for donating the embryo for research (5).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726839/#:~:text=However%2C%20human%20embryonic%20stem%20cell,the
%20destruction%20of%20human%20embryos.&text=As%20a%20matter%20of%20religious,embryo%20is%20therefore%20a
%20person.

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Gene Expression in Stem Cells

 totipotency: the ability of a cell to produce differentiated cells upon

Adding cells through cellular division

Stem cells are undifferentiated biological cells found in multicellular organisms,

Symmetric and asymmetric cell division

Symmetric and Asymmetric Division: This diagram illustrates stem cell

In principle, there are two mechanisms by which distinct properties may be

III. Embryonic Stem Cell Research

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