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Cited by 240Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

A Precarious Balance: Pluripotency Factors as Lineage Specifiers

Open access
Loh, Kyle M., Lim, Bing·2011·Cell Stem Cell
DOI 10.1016/j.stem.2011.03.013
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Abstract

Understanding the basis of the unrestricted multilineage differentiation potential of pluripotent cells will be of developmental and translational consequence. We propose that pluripotency transcription factors are lineage specifiers that direct commitment to specific fetal lineages. Individual factors bestow the ability to differentiate into particular cell types, and concomitant expression of multiple lineage specifiers within pluripotent cells enables differentiation into every fetal lineage. Moreover, we speculate that, rather than being an intrinsically stable "ground state," pluripotency is an inherently precarious condition in which rival lineage specifiers continually compete to specify differentiation along mutually exclusive lineages.

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  • Overlapping TF gradients accompany cellular differentiation in systems including exit from pluripotency, organogenesis, and tissue regeneration by adult stem cells.

    “Similar overlapping TF gradients accompany cellular differentiation in systems ranging from the exit from pluripotency5 over organogenesis6 to tissue regeneration by other adult stem cells.7,8”

    From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [5]

    The paper’s discussion of pluripotency-factor expression (indexed as Abstract; page unavailable) reports variation in Oct4 and Sox2 levels among embryonic stem cells and cites findings that changes in their levels can elicit differentiation. It proposes that competing factors influence lineage choice, but does not establish that overlapping TF gradients accompany exit from pluripotency. Citation 5 is attached to that part of the citing sentence, not to its separate claims about organogenesis or adult stem cells. (LLM, conf=0.83)

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Research works printed but not linked: 37

  1. [1]1. Canham, M.A. ∙ Sharov, A.A. ∙ Ko, M.S.H. ... PLoS Biol. 2010; 8:e1000379 Crossref Scopus (198) PubMed Google Scholar
  2. [2]2. Chng, Z. ∙ Teo, A. ∙ Pedersen, R.A. ... Cell Stem Cell. 2010; 6:59-70 Full Text Full Text (PDF) Scopus (109) PubMed Google Scholar
  3. [3]3. Davidson, E.H. Nature. 2010; 468:911-920 Crossref Scopus (434) PubMed Google Scholar
  4. [4]4. Enver, T. ∙ Greaves, M. Cell. 1998; 94:9-12 Full Text Full Text (PDF) Scopus (188) PubMed Google Scholar
  5. [5]5. Fiering, S. ∙ Northrop, J.P. ∙ Nolan, G.P. ... Genes Dev. 1990; 4:1823-1834 Crossref Scopus (230) PubMed Google Scholar
  6. [6]6. Graf, T. ∙ Enver, T. Nature. 2009; 462:587-594 Crossref Scopus (709) PubMed Google Scholar
  7. [7]7. Graf, T. ∙ Stadtfeld, M. Cell Stem Cell. 2008; 3:480-483 Full Text Full Text (PDF) Scopus (276) PubMed Google Scholar
  8. [8]8. Ivanova, N. ∙ Dobrin, R. ∙ Lu, R. ... Nature. 2006; 442:533-538 Crossref Scopus (815) PubMed Google Scholar
  9. [9]9. Jaenisch, R. ∙ Young, R. Cell. 2008; 132:567-582 Full Text Full Text (PDF) Scopus (1161) PubMed Google Scholar
  10. [10]10. Kobayashi, T. ∙ Mizuno, H. ∙ Imayoshi, I. ... Genes Dev. 2009; 23:1870-1875 Crossref Scopus (211) PubMed Google Scholar
  11. [11]11. Kopp, J.L. ∙ Ormsbee, B.D. ∙ Desler, M. ... Stem Cells. 2008; 26:903-911 Crossref Scopus (253) PubMed Google Scholar
  12. [12]12. Kunath, T. ∙ Saba-El-Leil, M.K. ∙ Almousailleakh, M. ... Development. 2007; 134:2895-2902 Crossref Scopus (626) PubMed Google Scholar
  13. [13]13. Lessard, J.A. ∙ Crabtree, G.R. Annu. Rev. Cell Dev. Biol. 2010; 26:503-532 Crossref Scopus (147) PubMed Google Scholar
  14. [14]14. Liber, D. ∙ Domaschenz, R. ∙ Holmqvist, P.-H. ... Cell Stem Cell. 2010; 7:114-126 Full Text Full Text (PDF) Scopus (67) PubMed Google Scholar
  15. [15]15. Lu, R. ∙ Yang, A. ∙ Jin, Y. J. Biol. Chem. 2011; 286:8425-8436 Full Text Full Text (PDF) Scopus (72) PubMed Google Scholar
  16. [16]16. Nichols, J. ∙ Chambers, I. ∙ Taga, T. ... Development. 2001; 128:2333-2339 Crossref PubMed Google Scholar
  17. [17]17. Nishiyama, A. ∙ Xin, L. ∙ Sharov, A.A. ... Cell Stem Cell. 2009; 5:420-433 Full Text Full Text (PDF) Scopus (157) PubMed Google Scholar
  18. [18]18. Niwa, H. ∙ Miyazaki, J. ∙ Smith, A.G. Nat. Genet. 2000; 24:372-376 Crossref Scopus (2995) PubMed Google Scholar
  19. [19]19. Niwa, H. ∙ Ogawa, K. ∙ Shimosato, D. ... Nature. 2009; 460:118-122 Crossref Scopus (711) PubMed Google Scholar
  20. [20]20. Ogawa, K. ∙ Saito, A. ∙ Matsui, H. ... J. Cell Sci. 2007; 120:55-65 Crossref Scopus (152) PubMed Google Scholar
  21. [21]21. Sato, N. ∙ Meijer, L. ∙ Skaltsounis, L. ... Nat. Med. 2004; 10:55-63 Crossref Scopus (1790) PubMed Google Scholar
  22. [22]22. Silva, J. ∙ Smith, A. Cell. 2008; 132:532-536 Full Text Full Text (PDF) Scopus (381) PubMed Google Scholar
  23. [23]23. Smith, A.G. Annu. Rev. Cell Dev. Biol. 2001; 17:435-462 Crossref Scopus (1060) PubMed Google Scholar
  24. [24]24. Smith, A. Cell. 2005; 123:757-760 Full Text Full Text (PDF) Scopus (26) PubMed Google Scholar
  25. [25]25. Smith, A.G. ∙ Nichols, J. ∙ Robertson, M. ... Dev. Biol. 1992; 151:339-351 Crossref Scopus (113) PubMed Google Scholar
  26. [26]26. Sun, C. ∙ Nakatake, Y. ∙ Akagi, T. ... Mol. Cell. Biol. 2009; 29:4574-4583 Crossref Scopus (61) PubMed Google Scholar
  27. [28]28. Tang, F. ∙ Barbacioru, C. ∙ Bao, S. ... Cell Stem Cell. 2010; 6:468-478 Full Text Full Text (PDF) Scopus (430) PubMed Google Scholar
  28. [29]29. Tay, S. ∙ Hughey, J.J. ∙ Lee, T.K. ... Nature. 2010; 466:267-271 Crossref Scopus (654) PubMed Google Scholar
  29. [30]30. Teo, A.K.K. ∙ Arnold, S.J. ∙ Trotter, M.W.B. ... Genes Dev. 2011; 25:238-250 Crossref Scopus (274) PubMed Google Scholar
  30. [31]31. Wray, J. ∙ Kalkan, T. ∙ Smith, A.G. Biochem. Soc. Trans. 2010; 38:1027-1032 Crossref Scopus (274) PubMed Google Scholar
  31. [32]32. Xu, J. ∙ Watts, J.A. ∙ Pope, S.D. ... Genes Dev. 2009; 23:2824-2838 Crossref Scopus (144) PubMed Google Scholar
  32. [33]33. Yamada, Y. ∙ Aoki, H. ∙ Kunisada, T. ... Cell Stem Cell. 2010; 6:10-15 Full Text Full Text (PDF) Scopus (51) PubMed Google Scholar
  33. [34]34. Ying, Q.L. ∙ Nichols, J. ∙ Chambers, I. ... Cell. 2003; 115:281-292 Full Text Full Text (PDF) Scopus (1769) PubMed Google Scholar
  34. [35]35. Ying, Q.-L. ∙ Wray, J. ∙ Nichols, J. ... Nature. 2008; 453:519-523 Crossref Scopus (2715) PubMed Google Scholar
  35. [36]36. Young, R.A. Cell. 2011; 144:940-954 Full Text Full Text (PDF) Scopus (936) PubMed Google Scholar
  36. [37]37. Yu, P. ∙ Pan, G. ∙ Yu, J. ... Cell Stem Cell. 2011; 8:326-334 Full Text Full Text (PDF) Scopus (203) PubMed Google Scholar
  37. [38]38. Zeineddine, D. ∙ Papadimou, E. ∙ Chebli, K. ... Dev. Cell. 2006; 11:535-546 Full Text Full Text (PDF) Scopus (150) PubMed Google Scholar

Cited by

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Authors
Loh, K. M., & Lim, B.
Affiliations
  • Genome Institute of Singapore (SG)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
  • Loh, Kyle M.
  • Lim, Bing
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2011-04
Volume
8
Issue
4
Pages
363-369
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2011.03.013
OpenAlex
W1964076580
Cited by
240
References
3
Citations by year
2026: 5 · 2025: 3 · 2024: 12 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 12 · 2018: 16 · 2017: 16 · 2016: 23 · 2015: 29 · 2014: 32 · 2013: 31 · 2012: 19
FWCI
10.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
pluripotency, pluripotency transcription factors, lineage specification, multilineage differentiation, differentiation commitment, ground state
MeSH terms
Cell Differentiation, Humans, Transcription Factors, Cell Lineage, Pluripotent Stem Cells

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