scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy

Although the hedgehog (HH) pathway is known to be deregulated in medulloblastoma, inhibitors of the pathway have shown disappointing clinical benefit. Using single-cell sequencing in a mouse model of the disease, the authors show that the response to the HH pathway inhibitor vismodegib is cell-type...

Full description

Bibliographic Details
Main Authors:	Jennifer Ocasio, Benjamin Babcock, Daniel Malawsky, Seth J. Weir, Lipin Loo, Jeremy M. Simon, Mark J. Zylka, Duhyeong Hwang, Taylor Dismuke, Marina Sokolsky, Elias P. Rosen, Rajeev Vibhakar, Jiao Zhang, Olivier Saulnier, Maria Vladoiu, Ibrahim El-Hamamy, Lincoln D. Stein, Michael D. Taylor, Kyle S. Smith, Paul A. Northcott, Alejandro Colaneri, Kirk Wilhelmsen, Timothy R. Gershon
Format:	Article
Language:	English
Published:	Nature Publishing Group 2019-12-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-019-13657-6

id	doaj-2fac3f5447844cbea3e21cfcf9b5423c
record_format	Article
spelling	doaj-2fac3f5447844cbea3e21cfcf9b5423c2021-05-11T12:24:32ZengNature Publishing GroupNature Communications2041-17232019-12-0110111710.1038/s41467-019-13657-6scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapyJennifer Ocasio0Benjamin Babcock1Daniel Malawsky2Seth J. Weir3Lipin Loo4Jeremy M. Simon5Mark J. Zylka6Duhyeong Hwang7Taylor Dismuke8Marina Sokolsky9Elias P. Rosen10Rajeev Vibhakar11Jiao Zhang12Olivier Saulnier13Maria Vladoiu14Ibrahim El-Hamamy15Lincoln D. Stein16Michael D. Taylor17Kyle S. Smith18Paul A. Northcott19Alejandro Colaneri20Kirk Wilhelmsen21Timothy R. Gershon22Department of Neurology, University of North Carolina School of MedicineDepartment of Neurology, University of North Carolina School of MedicineDepartment of Neurology, University of North Carolina School of MedicineDepartment of Neurology, University of North Carolina School of MedicineUNC Neuroscience Center, University of North Carolina School of MedicineUNC Neuroscience Center, University of North Carolina School of MedicineUNC Neuroscience Center, University of North Carolina School of MedicineUNC Eshelman School of Pharmacy, University of North Carolina School of MedicineDepartment of Neurology, University of North Carolina School of MedicineUNC Eshelman School of Pharmacy, University of North Carolina School of MedicineUNC Eshelman School of Pharmacy, University of North Carolina School of MedicineDepartment of Pediatrics, University of Colorado Anschutz Medical CampusDevelopmental & Stem Cell Biology Program, The Hospital for Sick ChildrenDevelopmental & Stem Cell Biology Program, The Hospital for Sick ChildrenDevelopmental & Stem Cell Biology Program, The Hospital for Sick ChildrenDepartment of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of TorontoDevelopmental & Stem Cell Biology Program, The Hospital for Sick ChildrenDepartment of Developmental Neurobiology, St. Jude Children’s Research HospitalDepartment of Developmental Neurobiology, St. Jude Children’s Research HospitalDepartment of Neurology, University of North Carolina School of MedicineDepartment of Neurology, University of North Carolina School of MedicineDepartment of Neurology, University of North Carolina School of MedicineAlthough the hedgehog (HH) pathway is known to be deregulated in medulloblastoma, inhibitors of the pathway have shown disappointing clinical benefit. Using single-cell sequencing in a mouse model of the disease, the authors show that the response to the HH pathway inhibitor vismodegib is cell-type specific.https://doi.org/10.1038/s41467-019-13657-6
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Jennifer Ocasio Benjamin Babcock Daniel Malawsky Seth J. Weir Lipin Loo Jeremy M. Simon Mark J. Zylka Duhyeong Hwang Taylor Dismuke Marina Sokolsky Elias P. Rosen Rajeev Vibhakar Jiao Zhang Olivier Saulnier Maria Vladoiu Ibrahim El-Hamamy Lincoln D. Stein Michael D. Taylor Kyle S. Smith Paul A. Northcott Alejandro Colaneri Kirk Wilhelmsen Timothy R. Gershon
spellingShingle	Jennifer Ocasio Benjamin Babcock Daniel Malawsky Seth J. Weir Lipin Loo Jeremy M. Simon Mark J. Zylka Duhyeong Hwang Taylor Dismuke Marina Sokolsky Elias P. Rosen Rajeev Vibhakar Jiao Zhang Olivier Saulnier Maria Vladoiu Ibrahim El-Hamamy Lincoln D. Stein Michael D. Taylor Kyle S. Smith Paul A. Northcott Alejandro Colaneri Kirk Wilhelmsen Timothy R. Gershon scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy Nature Communications
author_facet	Jennifer Ocasio Benjamin Babcock Daniel Malawsky Seth J. Weir Lipin Loo Jeremy M. Simon Mark J. Zylka Duhyeong Hwang Taylor Dismuke Marina Sokolsky Elias P. Rosen Rajeev Vibhakar Jiao Zhang Olivier Saulnier Maria Vladoiu Ibrahim El-Hamamy Lincoln D. Stein Michael D. Taylor Kyle S. Smith Paul A. Northcott Alejandro Colaneri Kirk Wilhelmsen Timothy R. Gershon
author_sort	Jennifer Ocasio
title	scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy
title_short	scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy
title_full	scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy
title_fullStr	scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy
title_full_unstemmed	scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy
title_sort	scrna-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to shh inhibitor therapy
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2019-12-01
description	Although the hedgehog (HH) pathway is known to be deregulated in medulloblastoma, inhibitors of the pathway have shown disappointing clinical benefit. Using single-cell sequencing in a mouse model of the disease, the authors show that the response to the HH pathway inhibitor vismodegib is cell-type specific.
url	https://doi.org/10.1038/s41467-019-13657-6
work_keys_str_mv	AT jenniferocasio scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT benjaminbabcock scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT danielmalawsky scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT sethjweir scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT lipinloo scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT jeremymsimon scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT markjzylka scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT duhyeonghwang scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT taylordismuke scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT marinasokolsky scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT eliasprosen scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT rajeevvibhakar scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT jiaozhang scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT oliviersaulnier scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT mariavladoiu scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT ibrahimelhamamy scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT lincolndstein scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT michaeldtaylor scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT kylessmith scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT paulanorthcott scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT alejandrocolaneri scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT kirkwilhelmsen scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy AT timothyrgershon scrnaseqinmedulloblastomashowscellularheterogeneityandlineageexpansionsupportresistancetoshhinhibitortherapy
_version_	1721444791740268544

scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy

Similar Items