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

Abstract 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 th...

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Autores principales:	Mee-Hae Kim, Yo Sugawara, Yukako Fujinaga, Masahiro Kino-oka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42e0863ce2254f54ad5c4b3f516412b7
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spelling	oai:doaj.org-article:42e0863ce2254f54ad5c4b3f516412b72021-12-02T16:07:58ZBotulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies10.1038/s41598-017-00083-12045-2322https://doaj.org/article/42e0863ce2254f54ad5c4b3f516412b72017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00083-1https://doaj.org/toc/2045-2322Abstract 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.Mee-Hae KimYo SugawaraYukako FujinagaMasahiro Kino-okaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mee-Hae Kim Yo Sugawara Yukako Fujinaga Masahiro Kino-oka Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
description	Abstract 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.
format	article
author	Mee-Hae Kim Yo Sugawara Yukako Fujinaga Masahiro Kino-oka
author_facet	Mee-Hae Kim Yo Sugawara Yukako Fujinaga Masahiro Kino-oka
author_sort	Mee-Hae Kim
title	Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
title_short	Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
title_full	Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
title_fullStr	Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
title_full_unstemmed	Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
title_sort	botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hipsc colonies
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/42e0863ce2254f54ad5c4b3f516412b7
work_keys_str_mv	AT meehaekim botulinumhemagglutininmediatedselectiveremovalofcellsdeviatingfromtheundifferentiatedstateinhipsccolonies AT yosugawara botulinumhemagglutininmediatedselectiveremovalofcellsdeviatingfromtheundifferentiatedstateinhipsccolonies AT yukakofujinaga botulinumhemagglutininmediatedselectiveremovalofcellsdeviatingfromtheundifferentiatedstateinhipsccolonies AT masahirokinooka botulinumhemagglutininmediatedselectiveremovalofcellsdeviatingfromtheundifferentiatedstateinhipsccolonies
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Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies

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