WordNet

having the ability to give rise to unlike cells; "embryonic stem cells are totipotent"
the ability of a cell to give rise to unlike cells and so to develop a new organism or part; "animal cells lose their totipotency at an early stage in embryonic development" (同)totipotence

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/16 23:01:14」(JST)

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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. Potency is taken from the Latin term "potens" which means "having power."

Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. These stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

Totipotency

Totipotency 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. Toti comes from the Latin totus which means "entirely."

It is possible for a fully differentiated cell to return to a state of totipotency.^[4] 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.^[5]

The human development model is one which can be used to describe how totipotent cells arise.^[6] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.^[7] 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), into cells of the cytotrophoblast layer or syncytiotrophoblast layer of the placenta. 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.^[8] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA binding proteins (RBPs) in determining development differences.^[9]

In September 2013, a team from the Spanish national Cancer Research Centre were able for the first time to make adult cells from mice retreat to the characteristics of embryonic stem cells thereby achieving totipotency.^[10]

Pluripotency

A: Human embryonic stem cells (cell colonies that are not yet differentiated).

B: Nerve cells

In cell biology, pluripotency (from the Latin plurimus, meaning very many, and potens, meaning having power)^[11] 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).^[12] However, cell pluripotency is a continuum, ranging from the completely pluripotent cell that can form every cell of the embryo proper, e.g., embyronic 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.^[13] 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.^[14] 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;^[15] this technique called reprogramming earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.^[16] 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.^[17] 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.^[18]

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.^[18]

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,^[13] 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,^[19] 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.^[20] 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.^[21]

Multipotency

Hematopoietic stem cells are an example of multipotency. When they differentiate into myeloid or lymphoid progenitor cells, they lose potency and become oligopotent cells with the ability to give rise to all cells of its lineage.

Multipotency describes progenitor cells which have the gene activation potential to differentiate into multiple, but limited cell types. For example, a multipotent blood stem cell is a hematopoietic cell — and this cell type can differentiate itself into several types of blood cell types like lymphocytes, monocytes, neutrophils, etc., but cannot 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 one case, fibroblasts were converted into functional neurons.^[20] In another case, human umbilical cord blood stem cells were converted into human neurons.^[22] Research is also focusing on converting multipotent cells into pluripotent cells. ^[23]

Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in cord blood,^[24] adipose tissue,^[25] cardiac cells,^[26] bone marrow, and mesenchymal stem cells (MSCs) which are found in the third molar.^[27]

MSCs may prove to be a good, reliable source for stem cells because of the ease in collection of molars at 8–10 years of age and before adult dental calcification. MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes.^[28]

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.^[1] 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.^[29] 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.^[30] A close synonym for unipotent cell is precursor cell.

References

^ ^a ^b Hans R. Schöler (2007). "The Potential of Stem Cells: An Inventory". In Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner. Human biotechnology as Social Challenge. Ashgate Publishing, Ltd. p. 28. ISBN 978-0-7546-5755-2.
^ "Stem Cell School: Glossary".
^ Mitalipov S, Wolf D; Wolf (2009). "Totipotency, pluripotency and nuclear reprogramming". Advances in Biochemical Engineering & Biotechnology 114: 185–99. Bibcode:2009esc..book..185M. doi:10.1007/10_2008_45. ISBN 978-3-540-88805-5. PMC 2752493. PMID 19343304.
^ Western P (2009). "Foetal germ cells: striking the balance between pluripotency and differentiation". Int. J. Dev. Biol. 53 (2–3): 393–409. doi:10.1387/ijdb.082671pw. PMID 19412894.
^ Sugimoto K, Gordon SP, Meyerowitz EM (April 2011). "Regeneration in plants and animals: dedifferentiation, transdifferentiation, or just differentiation?". Trends Cell Biol. 21 (4): 212–8. doi:10.1016/j.tcb.2010.12.004. PMID 21236679.
^ Seydoux G, Braun RE (December 2006). "Pathway to totipotency: lessons from germ cells". Cell 127 (5): 891–904. doi:10.1016/j.cell.2006.11.016. PMID 17129777.
^ Asch R, Simerly C, Ord T, Ord VA, Schatten G (July 1995). "The stages at which human fertilization arrests: microtubule and chromosome configurations in inseminated oocytes which failed to complete fertilization and development in humans". Hum. Reprod. 10 (7): 1897–906. PMID 8583008.
^ Ciosk, R.; Depalma, Michael; Priess, James R. (10 February 2006). "Translational Regulators Maintain Totipotency in the Caenorhabditis elegans Germline". Science 311 (5762): 851–853. Bibcode:2006Sci...311..851C. doi:10.1126/science.1122491. PMID 16469927.
^ Kedde M, Agami R (April 2008). "Interplay between microRNAs and RNA-binding proteins determines developmental processes". Cell Cycle 7 (7): 899–903. doi:10.4161/cc.7.7.5644. PMID 18414021.
^ Serrano, Manuel (2013-09-11). "Study published in Nature is another step towards regenerative medicine" (PDF). cnio.es. Retrieved 2013-12-11.
^ "Biology Online". Biology-Online.org. Retrieved 25 April 2013.
^ Binder, Marc D.; Hirokawa, Nobutaka; Uwe Windhorst, eds. (2009). Encyclopedia of neuroscience. Berlin: Springer. ISBN 978-3540237358.
^ ^a ^b Baker, Monya (2007-12-06). "Adult cells reprogrammed to pluripotency, without tumors". Nature Reports Stem Cells. doi:10.1038/stemcells.2007.124.
^ Stadtfeld, M.; Hochedlinger, K. (15 October 2010). "Induced pluripotency: history, mechanisms, and applications". Genes & Development 24 (20): 2239–2263. doi:10.1101/gad.1963910.
^ Takahashi, Kazutoshi; Yamanaka, Shinya (August 2006). "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors". Cell 126 (4): 663–676. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
^ "The Nobel Prize in Physiology or Medicine 2012". Nobelprize.org. Nobel Media AB 2013. Web. 28 Nov 2013.
^ Takahashi, Kazutoshi; Tanabe, Koji; Ohnuki, Mari; Narita, Megumi; Ichisaka, Tomoko; Tomoda, Kiichiro; Yamanaka, Shinya (1 November 2007). "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors". Cell 131 (5): 861–872. doi:10.1016/j.cell.2007.11.019. PMID 18035408.
^ ^a ^b Liang, Gaoyang; Zhang, Yi (18 December 2012). "Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective". Cell Research 23 (1): 49–69. doi:10.1038/cr.2012.175. PMC 3541668. PMID 23247625.
^ Choi, Charles. "Cell-Off: Induced Pluripotent Stem Cells Fall Short of Potential Found in Embryonic Version". Scientific American. Retrieved 25 April 2013.
^ ^a ^b Vierbuchen T; Wernig M; et al. (February 2010). "Direct conversion of fibroblasts to functional neurons by defined factors". Nature 463 (7284): 1035–41. Bibcode:2010Natur.463.1035V. doi:10.1038/nature08797. PMC 2829121. PMID 20107439.
^ Park, IH; Lerou, PH; Zhao, R; Huo, H; Daley, GQ (2008). "Generation of human-induced pluripotent stem cells.". Nature protocols 3 (7): 1180–6. doi:10.1038/nprot.2008.92. PMID 18600223.
^ Giorgetti A; Marchetto MC; Li M; et al. (July 2012). "Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc". Proc. Natl. Acad. Sci. U.S.A. 109 (31): 12556–61. Bibcode:2012PNAS..10912556G. doi:10.1073/pnas.1209523109. PMC 3412010. PMID 22814375.
^ Guan K; Nayernia K; Maier LS; et al. (April 2006). "Pluripotency of spermatogonial stem cells from adult mouse testis". Nature 440 (7088): 1199–203. Bibcode:2006Natur.440.1199G. doi:10.1038/nature04697. PMID 16565704.
^ Yong Zhao, Theodore Mazzone (Dec 2010). "Human cord blood stem cells and the journey to a cure for type 1 diabetes". Autoimmun Rev 10 (2): 103–107. doi:10.1016/j.autrev.2010.08.011. PMID 20728583.
^ Tallone T; Realini C; Böhmler A; et al. (April 2011). "Adult human adipose tissue contains several types of multipotent cells". J Cardiovasc Transl Res 4 (2): 200–10. doi:10.1007/s12265-011-9257-3. PMID 21327755.
^ Beltrami AP; Barlucchi L; Torella D; et al. (September 2003). "Adult cardiac stem cells are multipotent and support myocardial regeneration". Cell 114 (6): 763–76. doi:10.1016/S0092-8674(03)00687-1. PMID 14505575.
^ Ohgushi H, Arima N, Taketani T (December 2011). "[Regenerative therapy using allogeneic mesenchymal stem cells]". Nippon Rinsho (in Japanese) 69 (12): 2121–7. PMID 22242308.
^ Uccelli, Antonio; Moretta, Pistoia (September 2008). "Mesenchymal stem cells in health and disease". Nature Reviews 8 (9): 726–36. doi:10.1038/nri2395. PMID 19172693.
^ Ibelgaufts, Horst. "Cytokines & Cells Online Pathfinder Encyclopedia". Retrieved 25 April 2013.
^ "hepatoblast differentiation". GONUTS.

UpToDate Contents

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1. 肺外原発小細胞癌 extrapulmonary small cell cancer
2. 幹細胞の概要 overview of stem cells
3. 造血および幹細胞の機能の概要 overview of hematopoiesis and stem cell function
4. 組換え造血成長因子の概要 introduction to recombinant hematopoietic growth factors
5. 潜在性脊椎閉鎖不全症：病因およびタイプ closed spinal dysraphism pathogenesis and types

English Journal

Mechanisms of pluripotency in vivo and in vitro.

Posfai E1, Tam OH1, Rossant J2.Author information 1Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.2Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. Electronic address: janet.rossant@sickkids.ca.AbstractDuring the course of preimplantation development, the mammalian embryo develops from a single totipotent cell into a blastocyst that is composed of three distinct cell types. Two waves of lineage specification events take place, setting aside a pluripotent cell population, the epiblast, from extraembryonic tissues. The epiblast that will form the somatic cells and germ line of the adult organism remains pluripotent until gastrulation, which commences shortly after the embryo implants. The epiblast's remarkable property of pluripotency has been harnessed by researchers for decades through derivation of embryonic stem cells and epiblast stem cells. Both types of cells can self-renew indefinitely and still retain the ability of germ layer differentiation. However, a central conundrum to the field of stem cell biology is the extent to which these in vitro cultured cells represent their in vivo tissue of origin. In this review we discuss the development of in vivo pluripotency, and compare and contrast the role of signaling pathways and downstream transcription factors in embryo-derived stem cell types and their in vivo equivalent lineage counterparts.
Current topics in developmental biology.Curr Top Dev Biol.2014;107:1-37. doi: 10.1016/B978-0-12-416022-4.00001-9.
During the course of preimplantation development, the mammalian embryo develops from a single totipotent cell into a blastocyst that is composed of three distinct cell types. Two waves of lineage specification events take place, setting aside a pluripotent cell population, the epiblast, from extraem
PMID 24439801

Generating different epigenotypes.

Torres-Padilla ME.Author information Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, U de S, F-67404 Illkirch, CU de Strasbourg, France. Electronic address: metp@igbmc.fr.AbstractEmbryonic development is a specificity of metazoans. It starts with fertilization of the oocyte by a spermatozoon. Gametes then undergo intense chromatin remodelling and epigenetic reprogramming, which is necessary for reversion to a totipotent state in order to start a new developmental programme. This reprogramming process must occur with 100% efficiency in order to sustain development. The period following fertilization is therefore very rich and interesting in terms of chromatin remodelling. The latter underlies the reprogramming of the parental genomes, which is thought in turn to be essential to achieve the plasticity required to form all cell types in the new organism. However, this amazing capacity of the cells in the embryo to generate all cell types seems to be transient. Indeed, the ability of the early embryo to reprogramme somatic nuclei decreases as development proceeds. What makes the cells in the early embryo capable of supporting such a large degree of plasticity? These questions have remained largely unanswered and are central for understanding of cell plasticity, development and reprogramming. It is proposed that the basis of such plasticity relies on distinctive chromatin features that prevail during early embryogenesis and this hypothesis will be discussed in light of recent findings.
Reproductive biomedicine online.Reprod Biomed Online.2013 Dec;27(6):624-8. doi: 10.1016/j.rbmo.2013.07.016. Epub 2013 Aug 29.
Embryonic development is a specificity of metazoans. It starts with fertilization of the oocyte by a spermatozoon. Gametes then undergo intense chromatin remodelling and epigenetic reprogramming, which is necessary for reversion to a totipotent state in order to start a new developmental programme.
PMID 24080098

Single-cell profiling of epigenetic modifiers identifies PRDM14 as an inducer of cell fate in the mammalian embryo.

Burton A, Muller J, Tu S, Padilla-Longoria P, Guccione E, Torres-Padilla ME.Author information Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, Université de Strasbourg, F-67404 Illkirch, CU de Strasbourg, France.AbstractCell plasticity or potency is necessary for the formation of multiple cell types. The mechanisms underlying this plasticity are largely unknown. Preimplantation mouse embryos undergo drastic changes in cellular potency, starting with the totipotent zygote through to the formation of the pluripotent inner cell mass (ICM) and differentiated trophectoderm in the blastocyst. Here, we set out to identify and functionally characterize chromatin modifiers that define the transitions of potency and cell fate in the mouse embryo. Using a quantitative microfluidics approach in single cells, we show that developmental transitions are marked by distinctive combinatorial profiles of epigenetic modifiers. Pluripotent cells of the ICM are distinct from their differentiated trophectoderm counterparts. We show that PRDM14 is heterogeneously expressed in 4-cell-stage embryos. Forced expression of PRDM14 at the 2-cell stage leads to increased H3R26me2 and can induce a pluripotent ICM fate. Our results shed light on the epigenetic networks that govern cellular potency and identity in vivo.
Cell reports.Cell Rep.2013 Nov 14;5(3):687-701. doi: 10.1016/j.celrep.2013.09.044. Epub 2013 Oct 31.
Cell plasticity or potency is necessary for the formation of multiple cell types. The mechanisms underlying this plasticity are largely unknown. Preimplantation mouse embryos undergo drastic changes in cellular potency, starting with the totipotent zygote through to the formation of the pluripotent
PMID 24183668

Japanese Journal

Effects of Downregulating DNA Methyltransferase 1 Transcript by RNA Interference on DNA Methylation Status of the Satellite I Region and In Vitro Development of Bovine Somatic Cell Nuclear Transfer Embryos

Yamanaka Ken-ichi,Sakatani Miki,Kubota Kaiyu [他],BALBOULA Ahmed Zaky,SAWAI Ken,TAKAHASHI Masashi
The Journal of reproduction and development 57(3), 393-402, 2011-06-01
… For the successful production of cloned animals by somatic cell nuclear transfer (NT), the epigenetic status of the differentiated donor cell is reversed to an embryonic totipotent status. …
NAID 10029050711

Epigenetic Characteristics of Paternal Chromatin in Interspecies Zygotes

Barnetova Irena,Fulka Helena,Fulka Jr Josef
Journal of Reproduction and Development 56(6), 601-606, 2010
… Both the sperm and oocyte are terminally differentiated cells, but within a very short post-fertilization period, their genomes are converted into a totipotent zygote. …
NAID 130000305987

Acetylation Level of Histone H3 in Early Embryonic Stages Affects Subsequent Development of Miniature Pig Somatic Cell Nuclear Transfer Embryos

Yamanaka Ken-ichi,Sugimura Satoshi,Wakai Takuya [他],KAWAHARA Manabu,SATO Eimei
The Journal of reproduction and development 55(6), 638-644, 2009-12-01
… Successful cloning by somatic cell nuclear transfer (SCNT) requires a reprogramming process in which the epigenetic state of a differentiated donor nucleus must be converted into an embryonic totipotent state. …
NAID 10026322712