Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming.
Dppa2/4
Dux
SCNT
chemically induced pluripotent stem cells
zygotic genome activation
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 09 2020
03 09 2020
Historique:
received:
17
01
2020
revised:
27
06
2020
accepted:
02
07
2020
pubmed:
28
7
2020
medline:
28
4
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
Cloned animals generated by somatic cell nuclear transfer (SCNT) have been reported for many years; however, SCNT is extremely inefficient, and zygotic genome activation (ZGA) is required for SCNT-mediated somatic cell reprogramming. To identify candidate factors that facilitate ZGA in SCNT-mediated reprogramming, we performed siRNA-repressor and mRNA-inducer screenings, which reveal Dux, Dppa2, and Dppa4 as key factors enhancing ZGA in SCNT. We show that direct injection of ZGA inducers has no significant effect on SCNT blastocyst formation; however, following the establishment of an inducible Dux transgenic mouse model, we demonstrate that transient overexpression of Dux not only improves SCNT efficiency but also increases that of chemically induced pluripotent stem cell reprogramming. Moreover, transcriptome profiling reveals that Dux-treated SCNT embryos are similar to fertilized embryos. Furthermore, transient overexpression of Dux combined with inactivation of DNA methyltransferases (Dnmts) further promotes the full embryonic development of SCNT-derived animals. These findings enhance our understanding of ZGA-regulator function in somatic reprogramming.
Identifiants
pubmed: 32715614
doi: 10.15252/embr.202050054
pmc: PMC7506990
doi:
Substances chimiques
Dppa2 protein, mouse
0
Dppa4 protein, mouse
0
Nuclear Proteins
0
Transcription Factors
0
Banques de données
SRA
['SRR10201281', 'SRR10201280', 'SRR10201279', 'SRR10201278', 'SRR10201277', 'SRR10201285', 'SRR10201284', 'SRR10201283', 'SRR10201282', 'SRR11453944', 'SRR11453943', 'SRR11453942', 'SRR11453941', 'SRR11453940', 'SRR11453939']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e50054Subventions
Organisme : Genetically Modified Organisms Breeding Major Projects
ID : 2016ZX08007-002
Pays : International
Organisme : State Key Laboratory of R2BGL
Pays : International
Organisme : Inner Mongolia University Chief Scientist Program
Pays : International
Organisme : Inner Mongolia Autonomous Region Basic Research Project
Pays : International
Informations de copyright
© 2020 The Authors.
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