Cell potency

Cell potency is a cell's ability to differentiate into other cell types.[1][2]

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
Primordial germ cells
Pluripotency
Induced pluripotency
Naive vs. primed pluripotency states
Native pluripotency in plants
Multipotency
Oligopotency
Unipotency
See also Pluripotent, embryonic stem cells originate as
References inner mass cells within a blastocyst. These stem
cells can become any tissue in the body, excluding
External Links a placenta. Only the morula's cells are totipotent,
able to become all tissues and a placenta.

Totipotency
Totipotency (Lat. totipotentia, "ability for all [things]") is the ability of a single cell to divide and produce
all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.[3]
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 any extraembryonic cell. In contrast, pluripotent cells can
only differentiate into embryonic cells.[4][5]

A fully differentiated cell can return to a state of totipotency.[6] The conversion to totipotency is complex
and not fully understood. In 2011, research revealed that cells may differentiate not into a fully totipotent
cell, but instead into a "complex cellular variation" of totipotency.[7] Stem cells resembling totipotent
blastomeres from 2-cell stage embryos can arise spontaneously in mouse embryonic stem cell cultures[8][9]
and also can be induced to arise more frequently in vitro through down-regulation of the chromatin
assembly activity of CAF-1.[10]

The human development model can be used to describe how totipotent cells arise.[11] Human development
begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a
zygote.[12] 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 the morula 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 of embryonic 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.[13] Work with
zebrafish and mammals suggest a further interplay between miRNA and RNA-binding proteins (RBPs) in
determining development differences.[14]

Primordial germ cells

In mouse primordial germ cells, genome-wide reprogramming leading to totipotency involves erasure of
epigenetic imprints. Reprogramming is facilitated by active DNA demethylation involving the DNA base
excision repair enzymatic pathway.[15] This pathway entails erasure of CpG methylation (5mC) in
primordial germ cells via the initial conversion of 5mC to 5-hydroxymethylcytosine (5hmC), a reaction
driven by high levels of the ten-eleven dioxygenase enzymes TET-1 and TET-2.[16]

Pluripotency
In cell biology, pluripotency (Lat. pluripotentia, "ability for
many [things]")[17] 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), but not into extra-
embryonic tissues like the placenta.[18] 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, 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.[19] 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.[20] The ability to induce
A: Human embryonic stem cells (cell
cells into a pluripotent state was initially pioneered in 2006
colonies that are not yet differentiated).
using mouse fibroblasts and four transcription factors, Oct4,
B: Nerve cells
Sox2, Klf4 and c-Myc;[21] this technique, called
reprogramming, later earned Shinya Yamanaka and John
Gurdon the Nobel Prize in Physiology or Medicine.[22] This was then followed in 2007 by the successful
induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for
the induction of mouse cells.[23] These 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.[24]

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 of euchromatin found in ESCs.[24]

Due to their great similarity to ESCs, the medical and research communities are interested iPSCs. 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. 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,[19]
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,[25] hindering their use as ESCs
replacements.

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 (connective tissue cells) into fully functional neurons.[26] 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.[27]

Naive vs. primed pluripotency states

Findings with respect to epiblasts before and after implantation

have produced proposals for classifying pluripotency into two
distinct phases: "naive" and "primed".[28] 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 Naive human pluripotent stem cell
the other hand, several marked differences can be observed colony here seen growing on feeder
between the pre- and post-implantation epiblasts, such as their cells (mouse).
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 under random inactivation
in the early stage of the egg cylinder, known as X-inactivation.[29] 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,[30] such that they become
instructively specific according to the spatial organization.[31]
Another major difference is that post-implantation epiblast stem cells are unable to contribute to blastocyst
chimeras,[32] 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. Both ESCs and EpiSCs are derived from epiblasts but at difference phases of
development. Pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved
expression of Nanog, Fut4, and Oct-4 in EpiSCs,[33] until somitogenesis and can be reversed midway
through induced expression of Oct-4.[34]

Native pluripotency in plants

Un-induced pluripotency has been observed in root meristem tissue culture, especially by Kareem et al
2015, Kim et al 2018, and Rosspopoff et al 2017. This pluripotency is regulated by various regulators,
including PLETHORA 1 and PLETHORA 2; and PLETHORA 3, PLETHORA 5, and PLETHORA 7,
whose expression were found by Kareem to be auxin-provoked. (These are also known as PLT1, PLT2,
PLT3, PLT5, PLT7, and expressed by genes of the same names.) As of 2019, this is expected to open up
future research into pluripotency in root tissues.[35]

Multipotency
Multipotency is when progenitor cells have the gene activation
potential to differentiate into discrete cell types. For example, a
hematopoietic stem cell —and this cell type can differentiate itself
into several types of blood cell 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.

Research related to multipotent cells suggests that multipotent cells

may be capable of conversion into unrelated cell types. In another Hematopoietic stem cells are an
case, human umbilical cord blood stem cells were converted into example of multipotency. When they
human neurons.[36] There is also research on converting differentiate into myeloid or lymphoid
multipotent cells into pluripotent cells.[37] progenitor cells, they lose potency
and become oligopotent cells with
Multipotent cells are found in many, but not all human cell types. the ability to give rise to all cells of
Multipotent cells have been found in cord blood,[38] adipose its lineage.
tissue,[39] cardiac cells,[40] bone marrow, and mesenchymal stem
cells (MSCs) which are found in the third molar.[41]

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.[42]

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.[43] Examples of progenitor cells are vascular stem cells that have the capacity to
become both endothelial 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.[44] A close synonym for unipotent cell is precursor cell.

See also
Induced stem cells

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External Links
Blog on treatment therapy using pluripotent stem cells and pluripotent stem cell derived
exosomes (https://stemaidinstitute.com/blog)

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