CoChat
Sign Up
Cited by 87Pluripotent Stem Cells ResearchCellular Mechanics and InteractionsDevelopmental Biology and Gene Regulation

Non-muscle myosin II regulates survival threshold of pluripotent stem cells

Open access
Walker, Andrea, Su, Hua, Conti, Mary Anne, Harb, Nicole, Adelstein, Robert S., Sato, Noboru·2010·Nature Communications
DOI 10.1038/ncomms1074PMC PMC3430968
Open this paper in CoChat — free accountOpen PDF

Abstract

Human pluripotent stem (hPS) cells such as human embryonic stem (hES) and induced pluripotent stem (hiPS) cells are vulnerable under single cell conditions, which hampers practical applications; yet, the mechanisms underlying this cell death remain elusive. In this paper, we demonstrate that treatment with a specific inhibitor of non-muscle myosin II (NMII), blebbistatin, enhances the survival of hPS cells under clonal density and suspension conditions, and, in combination with a synthetic matrix, supports a fully defined environment for self-renewal. Consistent with this, genetically engineered mouse embryonic stem cells lacking an isoform of NMII heavy chain (NMHCII), or hES cells expressing a short hairpin RNA to knock down NMHCII, show greater viability than controls. Moreover, NMII inhibition increases the expression of self-renewal regulators Oct3/4 and Nanog, suggesting a mechanistic connection between NMII and self-renewal. These results underscore the importance of the molecular motor, NMII, as a novel target for chemically engineering the survival and self-renewal of hPS cells.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncomms1074

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • RhoA signalling might potentially contribute to cell death, because it can promote apoptosis in low-adhesion environments by increasing cell contractility.

    “RhoA signalling might also potentially contribute to cell death, because it can promote apoptosis in low-adhesion environments by increasing cell contractility, explaining why ROCK inhibitors are a standard component of media for stem cells and organoid isolation and maintenance in culture 77-81 .”

    From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [81]

    The Abstract reports that inhibiting non-muscle myosin II improves pluripotent stem-cell survival under single-cell growth conditions, and the Results report improved survival in suspension culture. But the Discussion says RhoA’s role as an upstream regulator of myosin II in this cell death remains to be determined; the paper does not establish that RhoA promotes apoptosis by increasing contractility in low-adhesion environments. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 40

  1. [1]Thomson JA Embryonic stem cell lines derived from human blastocysts Science 1998 282 1145 1147 9804556
  2. [2]Reubinoff BE Neural progenitors from human embryonic stem cells Nat. Biotechnol 2001 19 1134 1140 11731782
  3. [3]Takahashi K Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell 2007 131 861 872 18035408
  4. [4]Yu J Induced pluripotent stem cell lines derived from human somatic cells Science 2007 318 1917 1920 18029452
  5. [6]Amit M Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture Dev. Biol 2000 227 271 278 11071754
  6. [7]Rao M Scalable human ES culture for therapeutic use: propagation, differentiation, genetic modification and regulatory issues Gene Ther 2008 15 82 88 18004405
  7. [8]Pyle AD Lock LF Donovan PJ Neurotrophins mediate human embryonic stem cell survival Nat. Biotechnol 2006 24 344 350 16444268
  8. [9]Watanabe K A ROCK inhibitor permits survival of dissociated human embryonic stem cells Nat. Biotechnol 2007 25 681 686 17529971
  9. [10]Riento K Ridley AJ Rocks: multifunctional kinases in cell behaviour Nat. Rev. Mol. Cell Biol 2003 4 446 456 12778124
  10. [11]Xu C Feeder-free growth of undifferentiated human embryonic stem cells Nat. Biotechnol 2001 19 971 974 11581665
  11. [12]Mallon BS Park KY Chen KG Hamilton RS McKay RD Toward xeno-free culture of human embryonic stem cells Int. J. Biochem. Cell Biol 2006 38 1063 1075 16469522 PMC3449300
  12. [13]Ludwig TE Derivation of human embryonic stem cells in defined conditions Nat. Biotechnol 2006 24 185 187 16388305
  13. [14]Lu J Hou R Booth CJ Yang SH Snyder M Defined culture conditions of human embryonic stem cells Proc. Natl Acad. Sci. USA 2006 103 5688 5693 16595624 PMC1458634
  14. [15]Harb N Archer TK Sato N The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells PLoS ONE 2008 3 e3001 18714354 PMC2500174
  15. [16]Conti MA Adelstein RS Nonmuscle myosin II moves in new directions J. Cell Sci 2008 121 11 18 18096687
  16. [17]Matsumura F Regulation of myosin II during cytokinesis in higher eukaryotes Trends Cell Biol 2005 15 371 377 15935670
  17. [18]Mills JC Stone NL Erhardt J Pittman RN Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation J. Cell Biol 1998 140 627 636 9456322 PMC2140178
  18. [19]Croft DR Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration J. Cell Biol 2005 168 245 255 15657395 PMC2171584
  19. [20]Straight AF Dissecting temporal and spatial control of cytokinesis with a myosin II inhibitor Science 2003 299 1743 1747 12637748
  20. [21]Enver T Cellular differentiation hierarchies in normal and culture-adapted human embryonic stem cells Hum. Mol. Genet 2005 14 3129 3140 16159889
  21. [22]Stewart R Stojkovic M Lako M Mechanisms of self-renewal in human embryonic stem cells Eur. J. Cancer 2006 42 1257 1272 16630716
  22. [23]Hough SR Laslett AL Grimmond SB Kolle G Pera MF A continuum of cell states spans pluripotency and lineage commitment in human embryonic stem cells PLoS One 2009 4 e7708 19890402 PMC2768791
  23. [24]Conti MA Even-Ram S Liu C Yamada KM Adelstein RS Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice J. Biol. Chem 2004 279 41263 41266 15292239
  24. [25]Even-Ram S Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk Nat. Cell Biol 2007 9 299 309 17310241
  25. [26]Tullio AN Nonmuscle myosin II-B is required for normal development of the mouse heart Proc. Natl Acad. Sci. USA 1997 94 12407 12412 9356462 PMC24969
  26. [27]Sato N Molecular signature of human embryonic stem cells and its comparison with the mouse Dev. Biol 2003 260 404 413 12921741
  27. [28]Nichols J Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell 1998 95 379 391 9814708
  28. [29]Mitsui K The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells Cell 2003 113 631 642 12787504
  29. [30]Jaenisch R Young R Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming Cell 2008 132 567 582 18295576 PMC4142810
  30. [31]Sato N Meijer L Skaltsounis L Greengard P Brivanlou AH Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor Nat. Med 2004 10 55 63 14702635
  31. [32]Guo W Giancotti FG Integrin signalling during tumour progression Nat. Rev. Mol. Cell Biol 2004 5 816 826 15459662
  32. [33]Smith AG Embryo-derived stem cells: of mice and men Annu. Rev. Cell Dev. Biol 2001 17 435 462 11687496
  33. [34]Boiani M Scholer HR Regulatory networks in embryo-derived pluripotent stem cells Nat. Rev. Mol. Cell Biol 2005 6 872 884 16227977
  34. [35]Limouze J Straight AF Mitchison T Sellers JR Specificity of blebbistatin, an inhibitor of myosin II J. Muscle Res. Cell Motil 2004 25 337 341 15548862
  35. [36]Gomes ER Jani S Gundersen GG Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells Cell 2005 121 451 463 15882626
  36. [37]Ongusaha PP Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage Sci. Signal 2008 1 ra14 19036714 PMC2649725
  37. [38]Chan EM Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells Nat. Biotechnol 2009 27 1033 1037 19826408
  38. [39]Sato N Brivanlou AH Microarray approach to identify the signaling network responsible for self-renewal of human embryonic stem cells Methods Mol. Biol 2006 331 267 283 16881522
  39. [40]Sato N Brivanlou AH Manipulation of self-renewal in human embryonic stem cells through a novel pharmacological GSK-3 inhibitor Methods Mol. Biol 2006 331 115 128 16881513
  40. [41]Baker DE Adaptation to culture of human embryonic stem cells and oncogenesis in vivo Nat. Biotechnol 2007 25 207 215 17287758

Cited by

Sorted by citations

Authors
Walker, A., Su, H., Conti, M. A., Harb, N., Adelstein, R. S., & Sato, N.
Affiliations
  • University of California, Riverside (US)
  • National Institutes of Health (US)
Corresponding author
Sato, Noboru
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2010-09-07
Volume
1
Issue
1
Pages
71-71
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms1074
PMC
PMC3430968
OpenAlex
W2068811666
Cited by
87
References
1
Citations by year
2026: 3 · 2023: 2 · 2022: 7 · 2021: 12 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 8
FWCI
2.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (Z01HL004218)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
non-muscle myosin II, blebbistatin, pluripotent stem cells, human embryonic stem cells, induced pluripotent stem cells, cell survival, self-renewal, Oct4, Nanog, suspension culture, cell adhesion, molecular motors
MeSH terms
Animals, Cell Line, Cell Survival, Genetic Vectors, Heterocyclic Compounds, 4 or More Rings, Humans, Karyotyping, Lentivirus, In Situ Nick-End Labeling, Myosin Type II, RNA, Small Interfering, Pluripotent Stem Cells, Mice, Embryonic Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review