論文

査読有り 国際誌
2017年3月

Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies

SCIENTIFIC REPORTS
  • Mee-Hae Kim
  • ,
  • Yo Sugawara
  • ,
  • Yukako Fujinaga
  • ,
  • Masahiro Kino-oka

7
1
開始ページ
93
終了ページ
93
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-017-00083-1
出版者・発行元
NATURE PUBLISHING GROUP

The undifferentiated state of human induced pluripotent stem cells (hiPSCs) depends on their cell-cell and cell-substrate adhesions. In this study, we report that exposure to botulinum hemagglutinin (HA), an E-cadherin function-blocking agent, selectively removed cells that deviated from the undifferentiated state in hiPSC colonies. After HA treatment, cell-cell adhesion was disrupted, deviated cells detached from colony centers, and dividing cells filled these spaces. Because E-cadherin-mediated adhesion was disrupted in undifferentiated cells, stress-fiber formation and focal adhesions were diminished; however, these were subsequently restored, and the cells retained expression of undifferentiated stem cell markers and their differentiation potential. In contrast, actin structures and focal adhesions were lost from deviated cells, and they subsequently died. In undifferentiated and deviated cells, the cadherin/integrin-regulator Rap1 was localized at cell-cell adhesions and in the cytoplasm, respectively. Concurrent HA and Rap1-inhibitor treatment accelerated the deviated-cell detachment and delayed the recovery of hiPSC morphology, but this effect was significantly attenuated by co-treatment with Rap1 activator. Thus, Rap1 regulated E-cadherin-integrin interplay in hiPSC colonies exhibiting deviation, while HA-mediated selective removal of these deviated cells helped maintain the undifferentiated state in the remaining hiPSCs.


リンク情報
DOI
https://doi.org/10.1038/s41598-017-00083-1
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28273902
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428320
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000396942000010&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/s41598-017-00083-1
  • ISSN : 2045-2322
  • PubMed ID : 28273902
  • PubMed Central 記事ID : PMC5428320
  • Web of Science ID : WOS:000396942000010

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