Cell potency is acell's ability todifferentiate 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 withtotipotency to designate a cell with the most differentiation potential,pluripotency,multipotency,oligopotency, and finallyunipotency.
Totipotency (Latin:totipotentia,lit. 'ability for all [things]') is the ability of a singlecell to divide and produce all of the differentiated cells in anorganism.Spores andzygotes are examples of totipotent cells.[3]In the spectrum of cell potency, totipotency represents the cell with the greatestdifferentiation potential, being able to differentiate into anyembryonic cell, as well as anyextraembryonic tissue 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]
The human development model can be used to describe how totipotent cells arise.[8] Human development begins when asperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, azygote.[9] 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, orectoderm), or into cells of the placenta (cytotrophoblast orsyncytiotrophoblast). After reaching a 16-cell stage, the totipotent cells of themorula differentiate into cells that will eventually become either theblastocyst'sinner cell mass or the outertrophoblasts. 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 onCaenorhabditis elegans suggests that multiple mechanisms includingRNA regulation may play a role in maintaining totipotency at different stages of development in some species.[10] Work withzebrafish and mammals suggest a further interplay betweenmiRNA andRNA-binding proteins (RBPs) in determining development differences.[11]
In mouse primordialgerm cells,genome-wide reprogramming leading to totipotency involves erasure ofepigenetic imprints. Reprogramming is facilitated by activeDNA demethylation involving the DNAbase excision repair enzymatic pathway.[12] This pathway entails erasure ofCpG methylation (5mC) in primordial germ cells via the initial conversion of 5mC to5-hydroxymethylcytosine (5hmC), a reaction driven by high levels of the ten-eleven dioxygenase enzymesTET-1 andTET-2.[13]
In cell biology, pluripotency (Latin:pluripotentia,lit. 'ability for many [things]')[14] refers to a stem cell that has the potential todifferentiate into any of the threegerm layers:endoderm (gut, lungs and liver),mesoderm (muscle, skeleton, blood vascular, urogenital, dermis), orectoderm (nervous, sensory, epidermis), but not into extra-embryonic tissues like the placenta or yolk sac.[15]
Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs, are a type of pluripotentstem cell artificially derived from a non-pluripotent cell, typically an adultsomatic cell, by inducing a "forced" expression of certaingenes andtranscription factors.[16] 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.[17] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mousefibroblasts and four transcription factors,Oct4,Sox2,Klf4 and c-Myc;[18] this technique, calledreprogramming, later earnedShinya Yamanaka andJohn Gurdon the Nobel Prize in Physiology or Medicine.[19] 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.[20] 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, andgene expression.[21]
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.[21]
Due to their great similarity to ESCs, the medical and research communities are interested in 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 intoundifferentiatediPS cells was originally hailed as the end of thecontroversial use ofembryonic stem cells. However, iPSCs were found to be potentiallytumorigenic, and, despite advances,[16] were never approved for clinical stage research in the United States until recently. Currently, autologous iPSC-derived dopaminergic progenitor cells are used in trials for treating Parkinson's disease.[22] Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[23] hindering their use as ESCs replacements.
Somatic expression of combinedtranscription 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 functionalneurons.[24] This result challenges the terminal nature ofcellular 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 asin vitro models used for disease research.[25]
Findings with respect toepiblasts before and after implantation have produced proposals for classifying pluripotency into two states: "naive" and "primed", representing pre- and post-implantation epiblast, respectively.[26] Naive-to-primed continuum is controlled by reduction of Sox2/Oct4 dimerization on SoxOct DNA elements controlling naive pluripotency.[27] Primed pluripotent stem cells from different species could be reset to naive state using a cocktail containing Klf4 and Sox2 or "super-Sox" − a chimeric transcription factor with enhanced capacity to dimerize with Oct4.[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 under random inactivation in the early stage of the egg cylinder, known asX-inactivation.[28] During this development, the egg cylinder epiblast cells are systematically targeted byFibroblast 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 is that post-implantation epiblast stem cells are unable to contribute to blastocystchimeras,[31] which distinguishes them from other known pluripotent stem cells. Cell lines derived from such post-implantation epiblasts are referred to asepiblast-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 ofNanog,Fut4, andOct-4 in EpiSCs,[32] untilsomitogenesis and can be reversed midway through induced expression ofOct-4.[33]
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Un-induced pluripotency has been observed inroot 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, includingPLETHORA 1 andPLETHORA 2; andPLETHORA 3,PLETHORA 5, andPLETHORA 7, whose expression were found by Kareem to beauxin-provoked. (These are also known as PLT1, PLT2, PLT3, PLT5, PLT7, and expressed by genes of the same names.) As of 2019[update], this is expected to open up future research into pluripotency in root tissues.[34]
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Multipotency is whenprogenitor 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 likelymphocytes,monocytes,neutrophils, etc., but it is still ambiguous whetherHSC possess the ability to differentiate intobrain cells,bone cells or other non-blood cell types.[citation needed]
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.[35] There is also research on converting multipotent cells into pluripotent cells.[36]
Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found incord blood,[37] adipose tissue,[38] cardiac cells,[39]bone marrow, andmesenchymal stem cells (MSCs) which are found in thethird molar.[40]
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.[41]
In biology, oligopotency is the ability of progenitor cells to differentiate into a fewcell types. It is a degree ofpotency. 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.[42] Examples of progenitor cells are vascular stem cells that have the capacity to become bothendothelial or smooth muscle cells.
Incell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type.[43] It is currently unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate intohepatocytes (which constitute most of theliver) orcholangiocytes (epithelial cells of the bile duct), are bipotent.[44] A close synonym forunipotent cell isprecursor cell.
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