Show simple item record

dc.contributor.author
Baik, Ron
dc.contributor.author
Wyman, Stacia K.
dc.contributor.author
Kabir, Shaheen
dc.contributor.author
Corn, Jacob E.
dc.date.accessioned
2021-03-22T13:32:25Z
dc.date.available
2021-03-21T13:32:08Z
dc.date.available
2021-03-22T13:32:25Z
dc.date.issued
2021
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0247858
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/475547
dc.identifier.doi
10.3929/ethz-b-000475547
dc.description.abstract
Myeloproliferative neoplasms (MPNs) cause the over-production of blood cells such as erythrocytes (polycythemia vera) or platelets (essential thrombocytosis). JAK2 V617F is the most prevalent somatic mutation in many MPNs, but previous modeling of this mutation in mice relied on transgenic overexpression and resulted in diverse phenotypes that were in some cases attributed to expression level. CRISPR-Cas9 engineering offers new possibilities to model and potentially cure genetically encoded disorders via precise modification of the endogenous locus in primary cells. Here we develop “scarless” Cas9-based reagents to create and reverse the JAK2 V617F mutation in an immortalized human erythroid progenitor cell line (HUDEP-2), CD34+ adult human hematopoietic stem and progenitor cells (HSPCs), and immunophenotypic long-term hematopoietic stem cells (LT-HSCs). We find no overt in vitro increase in proliferation associated with an endogenous JAK2 V617F allele, but co-culture with wild type cells unmasks a competitive growth advantage provided by the mutation. Acquisition of the V617F allele also promotes terminal differentiation of erythroid progenitors, even in the absence of hematopoietic cytokine signaling. Taken together, these data are consistent with the gradually progressive manifestation of MPNs and reveals that endogenously acquired JAK2 V617F mutations may yield more subtle phenotypes as compared to transgenic overexpression models.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PLOS
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Genome editing to model and reverse a prevalent mutation associated with myeloproliferative neoplasms
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-03-04
ethz.journal.title
PLoS ONE
ethz.journal.volume
16
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0247858
en_US
ethz.size
24 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
San Francisco, CA
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09635 - Corn, Jacob / Corn, Jacob
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09635 - Corn, Jacob / Corn, Jacob
ethz.date.deposited
2021-03-21T13:32:17Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-03-22T13:32:35Z
ethz.rosetta.lastUpdated
2024-02-02T13:21:28Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Genome%20editing%20to%20model%20and%20reverse%20a%20prevalent%20mutation%20associated%20with%20myeloproliferative%20neoplasms&rft.jtitle=PLoS%20ONE&rft.date=2021&rft.volume=16&rft.issue=3&rft.spage=e0247858&rft.issn=1932-6203&rft.au=Baik,%20Ron&Wyman,%20Stacia%20K.&Kabir,%20Shaheen&Corn,%20Jacob%20E.&rft.genre=article&rft_id=info:doi/10.1371/journal.pone.0247858&
 Search print copy at ETH Library

Files in this item

Thumbnail

Publication type

Show simple item record