schliessen

Filtern

 

Bibliotheken

Modeling Wnt signaling by CRISPR-Cas9 genome editing facilitates neoplasia in human Barrett epithelial organoids

Primary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-ter... Full description

Journal Title: Cancer letters 2018-08-23, Vol.436, p.109-118
Main Author: Liu, Xi Xi
Other Authors: Cheng, Yulan Yulan , Abraham, John M John M , Wang, Zhixiong Zhixiong , Wang, Zhe Zhe , Ke, Xiquan Xiquan , Yan, Rong Rong , Shin, Eun Ji Eun Ji , Ngamruengphong, Saowanee Saowanee , Khashab, Mouen Mouen , Zhang, Guanjun Guanjun , McNamara, George George , Ewald, Andrew J Andrew J , Lin, DeChen DeChen , Liu, Zhengwen Zhengwen , Meltzer, Stephen J Stephen J
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
ID: ISSN: 0304-3835
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6152930
title: Modeling Wnt signaling by CRISPR-Cas9 genome editing facilitates neoplasia in human Barrett epithelial organoids
format: Article
creator:
  • Liu, Xi Xi
  • Cheng, Yulan Yulan
  • Abraham, John M John M
  • Wang, Zhixiong Zhixiong
  • Wang, Zhe Zhe
  • Ke, Xiquan Xiquan
  • Yan, Rong Rong
  • Shin, Eun Ji Eun Ji
  • Ngamruengphong, Saowanee Saowanee
  • Khashab, Mouen Mouen
  • Zhang, Guanjun Guanjun
  • McNamara, George George
  • Ewald, Andrew J Andrew J
  • Lin, DeChen DeChen
  • Liu, Zhengwen Zhengwen
  • Meltzer, Stephen J Stephen J
subjects:
  • Barrett esophagus
  • Cas9
  • CRISPR
  • neoplastic transformation
  • Organoids
  • Wnt signaling
ispartof: Cancer letters, 2018-08-23, Vol.436, p.109-118
description: Primary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC -knockout ( APC KO ) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APC KO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise presented in immortalized or cancer-derived cell lines.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0304-3835
fulltext: fulltext
issn:
  • 0304-3835
  • 1872-7980
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.6183143
LOCALfalse
PrimoNMBib
record
control
sourceidpubmedcentral
recordidTN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6152930
sourceformatXML
sourcesystemPC
sourcerecordidpubmedcentral_primary_oai_pubmedcentral_nih_gov_6152930
originalsourceidFETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_61529303
addsrcrecordideNqljM1KxDAURoMozvjzBi7yAq03TTttNy4sii4EGQWX5U57p71DmpQkI8zbO4ob18IHh48DR4gbBakCtbrdpR1aQzHNQFUpHKfKE7FUVZklZV3BqViChjzRlS4W4iKEHQAUeVmci4UGleeFypdifnE9GbaD_LBRBh4s_rzNQTbr57fXddJgqOVA1k0kqef4bbfYseGIkYK05GaDgVGyleN-Qivv0XuKUdLMcTzW0UjnB7SO-3AlzrZoAl3_8lLcPT68N0_JvN9M1Hdko0fTzp4n9IfWIbd_jeWxHdxnu1JFVmvQ_w58AQA9a68
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
display
typearticle
titleModeling Wnt signaling by CRISPR-Cas9 genome editing facilitates neoplasia in human Barrett epithelial organoids
sourceAlma/SFX Local Collection
creatorLiu, Xi Xi ; Cheng, Yulan Yulan ; Abraham, John M John M ; Wang, Zhixiong Zhixiong ; Wang, Zhe Zhe ; Ke, Xiquan Xiquan ; Yan, Rong Rong ; Shin, Eun Ji Eun Ji ; Ngamruengphong, Saowanee Saowanee ; Khashab, Mouen Mouen ; Zhang, Guanjun Guanjun ; McNamara, George George ; Ewald, Andrew J Andrew J ; Lin, DeChen DeChen ; Liu, Zhengwen Zhengwen ; Meltzer, Stephen J Stephen J
creatorcontribLiu, Xi Xi ; Cheng, Yulan Yulan ; Abraham, John M John M ; Wang, Zhixiong Zhixiong ; Wang, Zhe Zhe ; Ke, Xiquan Xiquan ; Yan, Rong Rong ; Shin, Eun Ji Eun Ji ; Ngamruengphong, Saowanee Saowanee ; Khashab, Mouen Mouen ; Zhang, Guanjun Guanjun ; McNamara, George George ; Ewald, Andrew J Andrew J ; Lin, DeChen DeChen ; Liu, Zhengwen Zhengwen ; Meltzer, Stephen J Stephen J
descriptionPrimary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC -knockout ( APC KO ) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APC KO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise presented in immortalized or cancer-derived cell lines.
identifier
0ISSN: 0304-3835
1EISSN: 1872-7980
2DOI: 10.1016/j.canlet.2018.08.017
3PMID: 30144514
languageeng
subjectBarrett esophagus ; Cas9 ; CRISPR ; neoplastic transformation ; Organoids ; Wnt signaling
ispartofCancer letters, 2018-08-23, Vol.436, p.109-118
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
search
creatorcontrib
0Liu, Xi Xi
1Cheng, Yulan Yulan
2Abraham, John M John M
3Wang, Zhixiong Zhixiong
4Wang, Zhe Zhe
5Ke, Xiquan Xiquan
6Yan, Rong Rong
7Shin, Eun Ji Eun Ji
8Ngamruengphong, Saowanee Saowanee
9Khashab, Mouen Mouen
10Zhang, Guanjun Guanjun
11McNamara, George George
12Ewald, Andrew J Andrew J
13Lin, DeChen DeChen
14Liu, Zhengwen Zhengwen
15Meltzer, Stephen J Stephen J
title
0Modeling Wnt signaling by CRISPR-Cas9 genome editing facilitates neoplasia in human Barrett epithelial organoids
1Cancer letters
descriptionPrimary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC -knockout ( APC KO ) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APC KO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise presented in immortalized or cancer-derived cell lines.
subject
0Barrett esophagus
1Cas9
2CRISPR
3neoplastic transformation
4Organoids
5Wnt signaling
issn
00304-3835
11872-7980
fulltexttrue
rsrctypearticle
creationdate2018
recordtypearticle
recordideNqljM1KxDAURoMozvjzBi7yAq03TTttNy4sii4EGQWX5U57p71DmpQkI8zbO4ob18IHh48DR4gbBakCtbrdpR1aQzHNQFUpHKfKE7FUVZklZV3BqViChjzRlS4W4iKEHQAUeVmci4UGleeFypdifnE9GbaD_LBRBh4s_rzNQTbr57fXddJgqOVA1k0kqef4bbfYseGIkYK05GaDgVGyleN-Qivv0XuKUdLMcTzW0UjnB7SO-3AlzrZoAl3_8lLcPT68N0_JvN9M1Hdko0fTzp4n9IfWIbd_jeWxHdxnu1JFVmvQ_w58AQA9a68
startdate20180823
enddate20180823
creator
0Liu, Xi Xi
1Cheng, Yulan Yulan
2Abraham, John M John M
3Wang, Zhixiong Zhixiong
4Wang, Zhe Zhe
5Ke, Xiquan Xiquan
6Yan, Rong Rong
7Shin, Eun Ji Eun Ji
8Ngamruengphong, Saowanee Saowanee
9Khashab, Mouen Mouen
10Zhang, Guanjun Guanjun
11McNamara, George George
12Ewald, Andrew J Andrew J
13Lin, DeChen DeChen
14Liu, Zhengwen Zhengwen
15Meltzer, Stephen J Stephen J
scope5PM
sort
creationdate20180823
titleModeling Wnt signaling by CRISPR-Cas9 genome editing facilitates neoplasia in human Barrett epithelial organoids
authorLiu, Xi Xi ; Cheng, Yulan Yulan ; Abraham, John M John M ; Wang, Zhixiong Zhixiong ; Wang, Zhe Zhe ; Ke, Xiquan Xiquan ; Yan, Rong Rong ; Shin, Eun Ji Eun Ji ; Ngamruengphong, Saowanee Saowanee ; Khashab, Mouen Mouen ; Zhang, Guanjun Guanjun ; McNamara, George George ; Ewald, Andrew J Andrew J ; Lin, DeChen DeChen ; Liu, Zhengwen Zhengwen ; Meltzer, Stephen J Stephen J
facets
frbrtype5
frbrgroupidcdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_61529303
rsrctypearticles
prefilterarticles
languageeng
creationdate2018
topic
0Barrett esophagus
1Cas9
2CRISPR
3neoplastic transformation
4Organoids
5Wnt signaling
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Liu, Xi Xi
1Cheng, Yulan Yulan
2Abraham, John M John M
3Wang, Zhixiong Zhixiong
4Wang, Zhe Zhe
5Ke, Xiquan Xiquan
6Yan, Rong Rong
7Shin, Eun Ji Eun Ji
8Ngamruengphong, Saowanee Saowanee
9Khashab, Mouen Mouen
10Zhang, Guanjun Guanjun
11McNamara, George George
12Ewald, Andrew J Andrew J
13Lin, DeChen DeChen
14Liu, Zhengwen Zhengwen
15Meltzer, Stephen J Stephen J
collectionPubMed Central (Full Participant titles)
jtitleCancer letters
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Liu, Xi Xi
1Cheng, Yulan Yulan
2Abraham, John M John M
3Wang, Zhixiong Zhixiong
4Wang, Zhe Zhe
5Ke, Xiquan Xiquan
6Yan, Rong Rong
7Shin, Eun Ji Eun Ji
8Ngamruengphong, Saowanee Saowanee
9Khashab, Mouen Mouen
10Zhang, Guanjun Guanjun
11McNamara, George George
12Ewald, Andrew J Andrew J
13Lin, DeChen DeChen
14Liu, Zhengwen Zhengwen
15Meltzer, Stephen J Stephen J
formatjournal
genrearticle
ristypeJOUR
atitleModeling Wnt signaling by CRISPR-Cas9 genome editing facilitates neoplasia in human Barrett epithelial organoids
jtitleCancer letters
date2018-08-23
risdate2018
volume436
spage109
epage118
pages109-118
issn0304-3835
eissn1872-7980
abstractPrimary organoid cultures generated from patient biopsies comprise a novel improved platform for disease modeling, being genetically stable and closely recapitulating in vivo scenarios. Barrett esophagus (BE) is the major risk factor for esophageal adenocarcinoma. There has been a dearth of long-term in vitro expansion models of BE neoplastic transformation. We generated a long-term virus-free organoid expansion model of BE neoplasia from patient biopsies. Both wild-type and paired APC -knockout ( APC KO ) BE organoids genome-edited by CRISPR-Cas9 showed characteristic goblet cell differentiation. Autonomous Wnt activation was confirmed in APC KO organoids by overexpression of Wnt target genes and nuclear-translocated β-catenin expression after withdrawal of Wnt-3A and R-spondin-1. Wnt-activated organoids demonstrated histologic atypia, higher proliferative and replicative activity, reduced apoptosis, and prolonged culturability. Wnt-activated organoids also showed sustained protrusive migration ability accompanied by disrupted basement membrane reorganization and integrity. This CRISPR-Cas9 editing human-derived organoid model recapitulates the critical role of aberrant Wnt/β-catenin signaling activation in BE neoplastic transformation. This system can be used to study other ‘driver’ pathway alterations in BE-associated neoplasia, avoiding signaling noise presented in immortalized or cancer-derived cell lines.
pmid30144514
doi10.1016/j.canlet.2018.08.017