Cell potency

Cell potency is a cell's ability to differentiate into other cell types[1][2][3] The more cell types a cell can differentiate into, the greater
its potency. Potency is also described as the gene activation potential within a cell, which, like a continuum, begins with totipotency
to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.

Contents
Totipotency
Pluripotency
Induced pluripotency
Naive vs. primed pluripotency states
Multipotency
Oligopotency
Unipotency
See also
References

Pluripotent, embryonic stem cells originate as inner

Totipotency mass cells within a blastocyst. These stem cells
can become any tissue in the body, excluding a
Totipotency (Lat. totipotentia, "ability for all [things]") is the ability placenta. Only the morula's cells are totipotent,
of a single cell to divide and produce all of the differentiated cells in able to become all tissues and a placenta.
an organism. Spores and zygotes are examples of totipotent cells.[4]
In the spectrum of cell potency, totipotency represents the cell with
the greatest differentiation potential, being able to differentiate into any embryonic cell, as well as extraembryonic cells. In contrast,
pluripotent cells can only differentiate into embryonic cells.[5][6]

It is possible for a fully differentiated cell to return to a state of totipotency.[7] This conversion to totipotency is complex, not fully
understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell,
but instead into a "complex cellular variation" of totipotency.[8] Stem cells resembling totipotent blastomeres from 2-cell stage
embryos can arise spontaneously in mouse embryonic stem cell cultures[9][10] and also can be induced to arise more frequently in
vitro through down-regulation of thechromatin assembly activity of CAF-1.[11]

The human development model is one which can be used to describe how totipotent cells arise.[12] Human development begins when
a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[13] In the first hours after
fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human
(endoderm, mesoderm, or ectoderm), or into cells of the placenta (cytotrophoblast or syncytiotrophoblast). After reaching a 16-cell
stage, the totipotent cells of themorula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the
outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to
specialize. The inner cell mass, the source ofembryonic stem cells, becomes pluripotent.

Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining
totipotency at different stages of development in some species.[14] Work with zebrafish and mammals suggest a further interplay
between miRNA and RNA-binding proteins(RBPs) in determining development differences.[15]

Pluripotency
In cell biology, pluripotency (Lat. pluripotentia, "ability for many
[things]")[16] refers to a stem cell that has the potential to differentiate into any
of the three germ layers: endoderm (interior stomach lining, gastrointestinal
tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm
(epidermal tissues and nervous system).[17] However, cell pluripotency is a
continuum, ranging from the completely pluripotent cell that can form every
cell of the embryo proper, e.g., embryonic stem cells and iPSCs (see below), to
the incompletely or partially pluripotent cell that can form cells of all three
germ layers but that may not exhibit all the characteristics of completely
pluripotent cells.

Induced pluripotency
Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs,
are a type of pluripotent stem cell artificially derived from a non-pluripotent
cell, typically an adult somatic cell, by inducing a "forced" expression of
certain genes and transcription factors.[18] These transcription factors play a
key role in determining the state of these cells and also highlights the fact that
these somatic cells do preserve the same genetic information as early
embryonic cells.[19] The ability to induce cells into a pluripotent state was
initially pioneered in 2006 using mouse fibroblasts and four transcription
factors, Oct4, Sox2, Klf4 and c-Myc;[20] this technique, called
reprogramming, earned Shinya Yamanaka and John Gurdon the Nobel Prize in
Physiology or Medicine 2012.[21] This was then followed in 2007 by the A: Human embryonic stem cells (cell
successful induction of human iPSCs derived from human dermal fibroblasts colonies that are not yet differentiated).
using methods similar to those used for the induction of mouse cells.[22] These B: Nerve cells
induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but
do not require the use of embryos. Some of the similarities between ESCs and
iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and
gene expression.[23]

Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has
been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire
the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that
found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also
consistent with the state ofeuchromatin found in ESCs.[23]

Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could
potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the
process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was
originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially
tumorigenic, and, despite advances,[18] were never approved for clinical stage research in the United States. Setbacks such as low
replication rates and early senescence have also been encountered when making iPSCs,[24] hindering their use as ESCs replacements.

Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined
somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly
convert mouse fibroblasts (skin cells) into fully functional neurons.[25] This result challenges the terminal nature of cellular
differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form
all kinds of tissue.
Some of the possible medical and therapeutic uses for iPSCs derived from patients include their use in cell and tissue transplants
without the risk of rejection that is commonly encountered. iPSCs can potentially replace animal models unsuitable as well as in vitro
models used for disease research.[26]

Naive vs. primed pluripotency states

Recent findings with respect to epiblasts before and after implantation have produced proposals for classifying pluripotency into two
distinct phases: "naive" and "primed".[27] The baseline stem cells commonly used in science that are referred as Embryonic stem
cells (ESCs) are derived from a pre-implantation epiblast; such epiblast is able to generate the entire fetus, and one epiblast cell is
able to contribute to all cell lineages if injected into another blastocyst. On the other hand, several marked differences can be
observed between the pre- and post-implantation epiblasts, such as their difference in morphology, in which the epiblast after
implantation changes its morphology into a cup-like shape called the "egg cylinder" as well as chromosomal alteration in which one
of the X-chromosomes undergoes random inactivation in the early stage of the egg cylinder, known as X-inactivation.[28] During this
development, the egg cylinder epiblast cells are systematically targeted by Fibroblast growth factors, Wnt signaling, and other
inductive factors via the surrounding yolk sac and the trophoblast tissue,[29] such that they become instructively specific according to
the spatial organization.[30] Another major difference that was observed, with respect to cell potency, is that post-implantation
epiblast stem cells are unable to contribute to blastocyst chimeras,[31] which distinguishes them from other known pluripotent stem
cells. Cell lines derived from such post-implantation epiblasts are referred to as epiblast-derived stem cells which were first derived
in laboratory in 2007; despite their nomenclature, that both ESCs and EpiSCs are derived from epiblasts, just at difference phases of
development, and that pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved expression of
Nanog, Fut4, and Oct-4 in EpiSCs,[32] until somitogenesis and can be reversed midway through induced expression ofOct-4.[33]

Multipotency
Multipotency describes progenitor cells which have the gene activation potential to
differentiate into discrete cell types. For example, a multipotent blood stem cell —
and this cell type can differentiate itself into several types of blood cell types like
lymphocytes, monocytes, neutrophils, etc., but it is still ambiguous whether HSC
possess the ability to differentiate into brain cells, bone cells or other non-blood cell
types.

New research related to multipotent cells suggests that multipotent cells may be
capable of conversion into unrelated cell types. In another case, human umbilical
cord blood stem cells were converted into human neurons.[34] Research is also Hematopoietic stem cells are an
focusing on converting multipotent cells intopluripotent cells.[35] example of multipotency. When they
differentiate into myeloid or lymphoid
Multipotent cells are found in many, but not all human cell types. Multipotent cells progenitor cells, they lose potency
have been found in cord blood,[36] adipose tissue,[37] cardiac cells,[38] bone marrow, and become oligopotent cells with
and mesenchymal stem cells(MSCs) which are found in thethird molar.[39] the ability to give rise to all cells of its
lineage.
MSCs may prove to be a valuable source for stem cells from molars at 8–10 years of
age, before adult dental calcification. MSCs can differentiate into osteoblasts,
chondrocytes, and adipocytes.[40]

Oligopotency
In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types. It is a degree of potency. Examples of
oligopotent stem cells are the lymphoid or myeloid stem cells.[2] A lymphoid cell specifically, can give rise to various blood cells
such as B and T cells, however, not to a different blood cell type like a red blood cell.[41] Examples of progenitor cells are vascular
stem cells that have the capacity to become bothendothelial or smooth muscle cells.
Unipotency
In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type. It is currently
unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or
cholangiocytes (epithelial cells of the bile duct), are bipotent.[42] A close synonym for unipotent cell is precursor cell.

See also
Induced stem cells

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