Cell potency is a general term which describes a stem cell's ability to differentiate into different cell types.[1] [2] Potency is known as the gene activation potential within a cell, and this potential is described along a continuum starting with totipotency and ending in unipotency. Totipotent cells are described as having 'high potency' whereas unipotent cells have 'low potency.'
Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The 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.
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Contents
- 1 Totipotency
- 2 Pluripotency
- 3 Multipotency
- 4 Oligopotency
- 5 Unipotency
- 6 References
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Totipotency
Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism, including extraembryonic tissues.[3] Totipotent cells include spores and zygotes. [4] In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential. Toti comes from the Latin totus which means "entirely."
Research has helped demonstrate that cells can regain totipotency[5] but research has also shown that regaining totipotency is complex. Instead of regaining full totipotency, cells may instead differentiate through a complex cellular variation of totipotency.[6]
Just how totipotent cells arise is described through the process of human development.[7] Consider first that human development begins when a sperm fertilizes an egg. The resulting fertilized egg creates a single totipotent cell, a zygote.[8] In the first hours after fertilization, this cell divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm) and into cells of the cytotrophoblast layer or syncytiotrophoblast layer of the placenta. After reaching the 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, is pluripotent, not totipotent.
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.[9] Work with zebrafish and mammals suggest a further an interplay between miRNA and RNA binding proteins (RBPs) in determining development differences.[10]
Pluripotency
Human embryonic stem cells
A: Cell colonies that are not yet differentiated.
B: Nerve cell
For substances having the capacity to produce several distinct biological responses see Pluripotency (biological compounds)
Main article: Stem Cell
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]
Induced pluripotency
Main article: Induced pluripotent stem cells
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 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc, in 2006.[15] 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.[16] 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.[17]
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.[17]
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,[18] 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; researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons.[19] 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.[20]
Multipotency
Further information: Progenitor cells
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 itself differentiate 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.[19] In another case, human umbilical cord blood stem cells were converted into human neurons.[21] Research is also focusing on converting multipotent cells into pluripotent cells [22]
Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in adipose tissue,[23] cardiac cells,[24] bone marrow, and mesenchymal stromal cells (MSCs) which are found in the third molar.[25]
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.[26]
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.[27] Examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells.
Unipotency
Further information: Precursor cell
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 in hepatocytes (which constitutes most of the liver) and cholangiocytes (epithelial cells of the bile duct), are bipotent.[28] 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.
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- ^ Mitalipov S, Wolf D (2009). "Totipotency, pluripotency and nuclear reprogramming.". Advances in Biochemical Engineering & Biotechnology 114: 185–99. doi:10.1007/10_2008_45. 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. (10 February 2006). "Translational Regulators Maintain Totipotency in the Caenorhabditis elegans Germline". Science 311 (5762): 851–853. doi:10.1126/science.1122491.
- ^ Kedde M, Agami R (April 2008). "Interplay between microRNAs and RNA-binding proteins determines developmental processes". Cell Cycle 7 (7): 899–903. PMID 18414021.
- ^ "Biology Online". Biology-Online.org. Retrieved 25 April 2013.
- ^ Binder, edited by Marc D.; Hirokawa, Nobutaka; (eds.), Uwe Windhorst (2009). Encyclopedia of neuroscience ([Online-Ausg.] ed.). 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 (NaN undefined NaN). "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.
- ^ 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.
- ^ 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.
- ^ 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. 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. 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. 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. doi:10.1038/nature04697. PMID 16565704.
- ^ 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. 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; Moretta, Pistoia (September 2008). "Mesenchymal stem cells in health and disease". Nature Reviews 8. doi:10.1038/nri2395. PMID 19172693.
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- ^ "hepatoblast differentiation". GONUTS.
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Cellular differentiation: Stem cells / progenitor cell
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| Sources/types |
Embryonic stem cells · Adult stem cells · Cancer stem cells · Induced pluripotent stem cells
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| Cell potency |
Totipotent (Zygote, Spore, Morula) · Pluripotent (Embryonic stem cell, Callus) · Multipotent (Progenitor cell: Endothelial stem cell, Hematopoietic stem cell, Mesenchymal stem cell, Neural stem cell) · Unipotent (Precursor cell)
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| Related articles |
Stem cell treatments · Stem cell controversy · Stem cell line · Stem cell laws · Stem cell laws and policy in the United States · Epigenetics in stem cell differentiation
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