Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

Abstract Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During earl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	C. E. Aban, A. Lombardi, G. Neiman, M. C. Biani, A. La Greca, A. Waisman, L. N. Moro, G. Sevlever, S. Miriuka, C. Luzzani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a808b5cf8e2d4310886af8574193af95
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a808b5cf8e2d4310886af8574193af95
record_format	dspace
spelling	oai:doaj.org-article:a808b5cf8e2d4310886af8574193af952021-12-02T15:23:28ZDownregulation of E-cadherin in pluripotent stem cells triggers partial EMT10.1038/s41598-021-81735-12045-2322https://doaj.org/article/a808b5cf8e2d4310886af8574193af952021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81735-1https://doaj.org/toc/2045-2322Abstract Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like phenotype. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize β-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.C. E. AbanA. LombardiG. NeimanM. C. BianiA. La GrecaA. WaismanL. N. MoroG. SevleverS. MiriukaC. LuzzaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q C. E. Aban A. Lombardi G. Neiman M. C. Biani A. La Greca A. Waisman L. N. Moro G. Sevlever S. Miriuka C. Luzzani Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT
description	Abstract Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like phenotype. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize β-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.
format	article
author	C. E. Aban A. Lombardi G. Neiman M. C. Biani A. La Greca A. Waisman L. N. Moro G. Sevlever S. Miriuka C. Luzzani
author_facet	C. E. Aban A. Lombardi G. Neiman M. C. Biani A. La Greca A. Waisman L. N. Moro G. Sevlever S. Miriuka C. Luzzani
author_sort	C. E. Aban
title	Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT
title_short	Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT
title_full	Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT
title_fullStr	Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT
title_full_unstemmed	Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT
title_sort	downregulation of e-cadherin in pluripotent stem cells triggers partial emt
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a808b5cf8e2d4310886af8574193af95
work_keys_str_mv	AT ceaban downregulationofecadherininpluripotentstemcellstriggerspartialemt AT alombardi downregulationofecadherininpluripotentstemcellstriggerspartialemt AT gneiman downregulationofecadherininpluripotentstemcellstriggerspartialemt AT mcbiani downregulationofecadherininpluripotentstemcellstriggerspartialemt AT alagreca downregulationofecadherininpluripotentstemcellstriggerspartialemt AT awaisman downregulationofecadherininpluripotentstemcellstriggerspartialemt AT lnmoro downregulationofecadherininpluripotentstemcellstriggerspartialemt AT gsevlever downregulationofecadherininpluripotentstemcellstriggerspartialemt AT smiriuka downregulationofecadherininpluripotentstemcellstriggerspartialemt AT cluzzani downregulationofecadherininpluripotentstemcellstriggerspartialemt
_version_	1718387282664226816

Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

Ejemplares similares