Totipotency

Totipotency, is the ability of a single stem cell to give rise to all the different cell types in an organism. In other words, it is the ability of a single cell to divide and produce all the differentiated cells of an organism.

This capacity is peculiar to embryonic stem cells up to a certain degree of development. Intermediate levels are called pluripotency and multipotency, if the cell can specialize respectively in all or some of the cell types that make up the organism. The lowest level is called unipotency, whereby the cell can transform into a single cell species typical of a tissue.

Spores and zygotes are examples of totipotent cells. On the spectrum of cellular potency, totipotency represents the cell with the greatest potential for differentiation, being able to differentiate into any embryonic cell, as well as any extraembryonic cell. In contrast, pluripotent cells can only differentiate into embryonic cells.

It is possible for a fully differentiated cell to return to a state of totipotency. This conversion to totipotency is complex, not fully understood, and the subject of recent research. Research in 2011 showed that cells can differentiate not into a fully totipotent cell, but instead into a “complex cell variation” of totipotency. Stem cells that resemble totipotent blastomeres from embryos at the 2-cell stage can arise spontaneously in mouse embryonic stem cell cultures and can also be induced to arise more frequently in vitro through down-regulation of CAF-1 chromatin assembly activity.

Human development is a model that can be used to describe how totipotent cells arise. Human development begins when a spermatozoon fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote. In the first few hours after fertilization, this zygote divides into identical totipotent cells, which can then develop into any of the three human germ layers (endoderm, mesoderm, or ectoderm), or into cells in the placenta (cytotrophoblast or syncytiotrophoblast). After reaching a 16-cell stage, the totipotent morula cells differentiate into cells that will eventually become the blastocyst’s inner cell mass or outer trophoblasts. About four days after fertilization and after several rounds of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.

Research in Caenorhabditis elegans suggests that multiple mechanisms, including RNA regulation, may play a role in maintaining totipotency at different stages of development in some species. Work in zebrafish and mammals suggests an additional interaction between miRNAs and RNA-binding proteins (RBPs) in determining developmental differences.

References

  1. Mitalipov S, Wolf D (2009). “Totipotency, pluripotency and nuclear reprogramming”. Engineering of Stem Cells. Advances in Biochemical Engineering/Biotechnology. 114. pp. 185–199. Bibcode:2009esc..book..185M. doi:10.1007/10_2008_45. ISBN 978-3-540-88805-5. PMC 2752493. PMID 19343304.
  2. Lodish, Harvey (2016). Molecular Cell Biology, 8th Ed. W. H. Freeman. pp. 975–977. ISBN 978-1319067748.
  3. 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.
  4. Sugimoto K, Gordon SP, Meyerowitz EM (April 2011). “Regeneration in plants and animals: dedifferentiation, transdifferentiation, or just differentiation?”. Trends Cell Biol. 21 (4): 212–218. doi:10.1016/j.tcb.2010.12.004. PMID 21236679.
  5. Macfarlan T.S.; Gifford W.D.; Driscoll S.; Lettieri K.; Rowe H.M.; Bonanomi D.; Firth A.; Singer O.; Trono D. & Pfaff S.L. (2012). “Embryonic stem cell potency fluctuates with endogenous retrovirus activity”. Nature. 487 (7405): 57–63. Bibcode:2012Natur.487…57M. doi:10.1038/nature11244. PMC 3395470. PMID 22722858.
  6. Morgani S.M.; Canham M.A.; Nichols J.; Sharov A.A.; Migueles R.P.; Ko M.S. & Brickman J.M. (2013). “Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions”. Cell Rep. 3 (6): 1945–1957. doi:10.1016/j.celrep.2013.04.034. PMC 3701323. PMID 23746443.
  7. Ishiuchi T.; Enriquez-Gasca R.; Mizutani E.; Boskovic A.; Ziegler-Birling C.; Rodriguez-Terrones D.; Wakayama T.; Vaquerizas J.M. & Torres-Padilla M.E. (2015). “Early embryonic-like cells are induced by downregulating replication dependent chromatin assembly”. Nat Struct Mol Biol. 22 (9): 662–671. doi:10.1038/nsmb.3066. PMID 26237512. S2CID 837230.
  8. 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. S2CID 16988032.
  9. 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): 1897–1906. doi:10.1093/oxfordjournals.humrep.a136204. PMID 8583008.
  10. ^ 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. S2CID 130017.
  11. 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.