Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue

Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoi...

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Autores: Costales Carrera, Alba, Fernández Barral, Asunción, Bustamante Madrid, Pilar, Domínguez, Orlando, Guerra Pastrián, Laura, Cantero Cid, Ramón, del Peso, Luis, Burgos, Aurora, Barbáchano, Antonio, Muñoz, Alberto
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/714880
Acesso em linha:http://hdl.handle.net/10486/714880
https://dx.doi.org/10.3390/cancers12082302
Access Level:acceso abierto
Palavra-chave:colorectal cancer
patient-derived organoids
rectal tumors
stem cells
vitamin D
Medicina
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spelling Comparative study of organoids from patient-derived normal and tumor colon and rectal tissueCostales Carrera, AlbaFernández Barral, AsunciónBustamante Madrid, PilarDomínguez, OrlandoGuerra Pastrián, LauraCantero Cid, Ramóndel Peso, LuisBurgos, AuroraBarbáchano, AntonioMuñoz, Albertocolorectal cancerpatient-derived organoidsrectal tumorsstem cellsvitamin DMedicinaColon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoidsThis research was founded by Agencia Estatal de Investigación (PID2019-104867RB-I00/AEI/10.13039/501100011033), Agencia Estatal de Investigación-Fondo Europeo de Desarrollo Regional (SAF2016-76377-R, MINECO/AEI/FEDER, UE), Ministerio de Economía y Competitividad (SAF2017-90604-REDT), Instituto de Salud Carlos III—Fondo Europeo de Desarrollo Regional (CIBERONC, CB16/12/00273; CIBERES, CB15/00037), and Mutua MadrileñaMDPIDepartamento de BioquímicaFacultad de Medicina20202020-08-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/714880https://dx.doi.org/10.3390/cancers12082302reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7148802026-06-23T12:46:27Z
dc.title.none.fl_str_mv Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
title Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
spellingShingle Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
Costales Carrera, Alba
colorectal cancer
patient-derived organoids
rectal tumors
stem cells
vitamin D
Medicina
title_short Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
title_full Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
title_fullStr Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
title_full_unstemmed Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
title_sort Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue
dc.creator.none.fl_str_mv Costales Carrera, Alba
Fernández Barral, Asunción
Bustamante Madrid, Pilar
Domínguez, Orlando
Guerra Pastrián, Laura
Cantero Cid, Ramón
del Peso, Luis
Burgos, Aurora
Barbáchano, Antonio
Muñoz, Alberto
author Costales Carrera, Alba
author_facet Costales Carrera, Alba
Fernández Barral, Asunción
Bustamante Madrid, Pilar
Domínguez, Orlando
Guerra Pastrián, Laura
Cantero Cid, Ramón
del Peso, Luis
Burgos, Aurora
Barbáchano, Antonio
Muñoz, Alberto
author_role author
author2 Fernández Barral, Asunción
Bustamante Madrid, Pilar
Domínguez, Orlando
Guerra Pastrián, Laura
Cantero Cid, Ramón
del Peso, Luis
Burgos, Aurora
Barbáchano, Antonio
Muñoz, Alberto
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Bioquímica
Facultad de Medicina
dc.subject.none.fl_str_mv colorectal cancer
patient-derived organoids
rectal tumors
stem cells
vitamin D
Medicina
topic colorectal cancer
patient-derived organoids
rectal tumors
stem cells
vitamin D
Medicina
description Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-08-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/714880
https://dx.doi.org/10.3390/cancers12082302
url http://hdl.handle.net/10486/714880
https://dx.doi.org/10.3390/cancers12082302
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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