Editing Embryonic stem cell (section)

==Properties==
[[File:Ips cells.png|thumb|IPS Cell ]]
[[File:The transcriptome of pluripotent cells..jpg|thumb|The transcriptome of embryonic stem cells]]
Embryonic stem cells (ESCs), derived from the blastocyst stage of early mammalian embryos, are distinguished by their ability to differentiate into any embryonic cell type and by their ability to self-renew. It is these traits that makes them valuable in the scientific and medical fields. ESCs have a normal [[karyotype]], maintain high [[telomerase]] activity, and exhibit remarkable long-term [[cell growth|proliferative]] potential.<ref name=sc>{{cite journal|doi=10.1126/science.282.5391.1145|pmid=9804556|title=Embryonic Stem Cell Lines Derived from Human Blastocysts|journal=Science|volume=282|issue=5391|pages=1145–7|year=1998|last1=Thomson|first1=J. A.|last2=Itskovitz-Eldor|first2=J|last3=Shapiro|first3=S. S.|last4=Waknitz|first4=M. A.|last5=Swiergiel|first5=J. J.|last6=Marshall|first6=V. S.|last7=Jones|first7=J. M.|bibcode=1998Sci...282.1145T|doi-access=free}}</ref>

=== Pluripotent ===

Embryonic stem cells of the inner cell mass are [[Cell potency#Pluripotency|pluripotent]], meaning they are able to [[Cellular differentiation|differentiate]] to generate primitive ectoderm, which ultimately differentiates during [[gastrulation]] into all derivatives of the three primary [[germ layer]]s: [[ectoderm]], [[endoderm]], and [[mesoderm]]. These germ layers generate each of the more than 220 [[List of distinct cell types in the adult human body|cell types]] in the adult human body. When provided with the appropriate signals, ESCs initially form [[precursor cells]] that in subsequently differentiate into the desired cell types. Pluripotency distinguishes embryonic stem cells from [[adult stem cell]]s, which are [[multipotent]] and can only produce a limited number of cell types.

=== Self renewal and repair of structure  ===

Under defined conditions, embryonic stem cells are capable of self-renewing indefinitely in an undifferentiated state. Self-renewal conditions must prevent the cells from clumping and maintain an environment that supports an unspecialized state.<ref>{{cite journal |author=Ying |title=BMP Induction of Id Proteins Suppresses Differentiation and Sustains Embryonic Stem Cell Self-Renewal in Collaboration with STAT3 |journal=Cell |volume=115 |issue= 3|pages= 281–292 |year=2003 |pmid= 14636556|doi=10.1016/S0092-8674(03)00847-X |last2=Nichols |first2=J |last3=Chambers |first3=I |last4=Smith |first4=A|s2cid=7201396 |doi-access=free }}</ref> Typically this is done in the lab with media containing [[fetal bovine serum|serum]] and [[leukemia inhibitory factor]] or serum-free media supplements with two inhibitory drugs ("2i"), the [[MEK inhibitor]] PD03259010 and [[GSK-3 inhibitor]] CHIR99021.<ref>{{cite journal|pmid=25288119|year=2014|last1=Martello|first1=G.|title=The nature of embryonic stem cells|journal=Annual Review of Cell and Developmental Biology|volume=30|pages=647–75|last2=Smith|first2=A.|doi=10.1146/annurev-cellbio-100913-013116|doi-access=free}}</ref>

=== Growth ===

ESCs divide very frequently due to a shortened [[G1 phase]] in their [[cell cycle]]. Rapid [[cell division]] allows the cells to quickly grow in number, but not size, which is important for early embryo development. In ESCs, [[cyclin A]] and [[cyclin E]] proteins involved in the [[G1/S transition]] are always expressed at high levels.<ref name="Boward">{{cite journal|pmid=26889666|pmc=5201256|year=2016|last1=Boward|first1=B.|title=Concise Review: Control of Cell Fate Through Cell Cycle and Pluripotency Networks|journal=Stem Cells|volume=34|issue=6|pages=1427–36|last2=Wu|first2=T.|last3=Dalton|first3=S.|doi=10.1002/stem.2345}}</ref> [[Cyclin-dependent kinase]]s such as [[CDK2]] that promote cell cycle progression are overactive, in part due to downregulation of their inhibitors.<ref>{{cite journal|pmid=15703208|pmc=1073679|year=2005|last1=White|first1=J.|title=Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation|journal=Molecular Biology of the Cell|volume=16|issue=4|pages=2018–27|last2=Stead|first2=E.|last3=Faast|first3=R.|last4=Conn|first4=S.|last5=Cartwright|first5=P.|last6=Dalton|first6=S.|doi=10.1091/mbc.e04-12-1056}}</ref> [[Retinoblastoma protein]]s that inhibit the [[transcription factor]] [[E2F]] until the cell is ready to enter [[S phase]] are hyperphosphorylated and inactivated in ESCs, leading to continual expression of proliferation genes.<ref name="Boward" /> These changes result in accelerated cycles of cell division. Although high expression levels of pro-proliferative proteins and a shortened G1 phase have been linked to maintenance of pluripotency,<ref>{{Cite journal|last1=Ter Huurne|first1=Menno|last2=Stunnenberg|first2=Hendrik G.|date=21 April 2021|title=G1-phase progression in pluripotent stem cells|journal=Cellular and Molecular Life Sciences|volume=21|issue=10|pages=4507–4519|doi=10.1007/s00018-021-03797-8|issn=1875-9777|pmid=33884444|pmc=8195903|doi-access=free}}</ref><ref>{{Cite journal|last1=Singh|first1=Amar M.|last2=Dalton|first2=Stephen|date=2009-08-07|title=The cell cycle and Myc intersect with mechanisms that regulate pluripotency and reprogramming|journal=Cell Stem Cell|volume=5|issue=2|pages=141–149|doi=10.1016/j.stem.2009.07.003|issn=1875-9777|pmc=2909475|pmid=19664987}}</ref> ESCs grown in serum-free 2i conditions do express hypo-phosphorylated active Retinoblastoma proteins and have an elongated G1 phase.<ref>{{Cite journal|last1=Ter Huurne|first1=Menno|last2=Chappell|first2=James|last3=Dalton|first3=Stephen|last4=Stunnenberg|first4=Hendrik G.|date=5 October 2017|title=Distinct Cell-Cycle Control in Two Different States of Mouse Pluripotency|journal=Cell Stem Cell|volume=21|issue=4|pages=449–455.e4|doi=10.1016/j.stem.2017.09.004|issn=1875-9777|pmc=5658514|pmid=28985526}}</ref> Despite this difference in the cell cycle when compared to ESCs grown in media containing serum these cells have similar pluripotent characteristics.<ref>{{Cite journal|last1=Ying|first1=Qi-Long|last2=Wray|first2=Jason|last3=Nichols|first3=Jennifer|last4=Batlle-Morera|first4=Laura|last5=Doble|first5=Bradley|last6=Woodgett|first6=James|last7=Cohen|first7=Philip|last8=Smith|first8=Austin|date=2008-05-22|title=The ground state of embryonic stem cell self-renewal|journal=Nature|volume=453|issue=7194|pages=519–523|doi=10.1038/nature06968|issn=1476-4687|pmc=5328678|pmid=18497825|bibcode=2008Natur.453..519Y}}</ref> Pluripotency factors [[Oct4]] and [[Homeobox protein NANOG|Nanog]] play a role in transcriptionally regulating the embryonic stem cell cycle.<ref>{{cite journal|pmid=19968627|pmc=2825734|year=2010|last1=Lee|first1=J.|title=Oct-4 controls cell-cycle progression of embryonic stem cells|journal=The Biochemical Journal|volume=426|issue=2|pages=171–81|last2=Go|first2=Y.|last3=Kang|first3=I.|last4=Han|first4=Y. M.|last5=Kim|first5=J.|doi=10.1042/BJ20091439}}</ref><ref>{{cite journal|pmid=19139263|pmc=2615089|year=2009|last1=Zhang|first1=X.|title=A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A|journal=The Journal of Cell Biology|volume=184|issue=1|pages=67–82|last2=Neganova|first2=I.|last3=Przyborski|first3=S.|last4=Yang|first4=C.|last5=Cooke|first5=M.|last6=Atkinson|first6=S. P.|last7=Anyfantis|first7=G.|last8=Fenyk|first8=S.|last9=Keith|first9=W. N.|last10=Hoare|first10=S. F.|last11=Hughes|first11=O.|last12=Strachan|first12=T.|last13=Stojkovic|first13=M.|last14=Hinds|first14=P. W.|last15=Armstrong|first15=L.|last16=Lako|first16=M.|doi=10.1083/jcb.200801009}}</ref>

=== Uses ===

Due to their plasticity and potentially unlimited capacity for self-renewal, embryonic [[Stem-cell therapy|stem cell therapies]] have been proposed for [[regenerative medicine]] and tissue replacement after injury or disease. Pluripotent stem cells have shown promise in treating a number of varying conditions, including but not limited to: [[spinal cord injuries]], [[age related macular degeneration]], [[diabetes]], [[neurodegenerative disorders]] (such as [[Parkinson's disease]]), [[AIDS]], etc.<ref>{{cite journal |last1=Mahla |first1=Ranjeet |title=Stem Cell Applications in Regenerative Medicine and Disease Therapeutics |journal=International Journal of Cell Biology |volume=2016 |date=July 19, 2016 |pages=6940283 |doi=10.1155/2016/6940283 |pmid=27516776|pmc=4969512 |doi-access=free }}</ref> In addition to their potential in regenerative medicine, embryonic stem cells provide a possible alternative source of tissue/organs which serves as a possible solution to the donor shortage dilemma. There are some ethical controversies surrounding this though (see '''Ethical debate''' section below). Aside from these uses, ESCs can also be used for research on early human development, certain genetic disease, and ''in vitro'' [[toxicology]] testing.<ref name=sc/>