Transient DUX4 expression in human embryonic stem cells induces blastomere-like expression program that is marked by SLC34A2

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Yoshihara , M , Kirjanov , I , Nykänen , S , Sokka , J , Weltner , J , Lundin , K , Gawriyski , L , Jouhilahti , E-M , Varjosalo , M , Tervaniemi , M H , Otonkoski , T , Trokovic , R , Katayama , S , Vuoristo , S & Kere , J 2022 , ' Transient DUX4 expression in human embryonic stem cells induces blastomere-like expression program that is marked by SLC34A2 ' , Stem cell reports , vol. 17 , no. 7 , pp. 1743-1756 . https://doi.org/10.1016/j.stemcr.2022.06.002

Title: Transient DUX4 expression in human embryonic stem cells induces blastomere-like expression program that is marked by SLC34A2
Author: Yoshihara, Masahito; Kirjanov, Ida; Nykänen, Sonja; Sokka, Joonas; Weltner, Jere; Lundin, Karolina; Gawriyski, Lisa; Jouhilahti, Eeva-Mari; Varjosalo, Markku; Tervaniemi, Mari H.; Otonkoski, Timo; Trokovic, Ras; Katayama, Shintaro; Vuoristo, Sanna; Kere, Juha
Contributor organization: HUS Gynecology and Obstetrics
Department of Obstetrics and Gynecology
STEMM - Stem Cells and Metabolism Research Program
Faculty of Medicine
University of Helsinki
Institute of Biotechnology
Centre of Excellence in Stem Cell Metabolism
Biosciences
Molecular Systems Biology
Research Programs Unit
Clinicum
Children's Hospital
Helsinki One Health (HOH)
Timo Pyry Juhani Otonkoski / Principal Investigator
HUS Children and Adolescents
Juha Kere / Principal Investigator
Date: 2022-07-12
Language: eng
Number of pages: 14
Belongs to series: Stem cell reports
ISSN: 2213-6711
DOI: https://doi.org/10.1016/j.stemcr.2022.06.002
URI: http://hdl.handle.net/10138/346605
Abstract: Embryonic genome activation (EGA) is critical for embryonic development. However, our understanding of the regulatory mechanisms of human EGA is still incomplete. Human embryonic stem cells (hESCs) are an established model for studying developmental processes, but they resemble epiblast and are sub-optimal for modeling EGA. DUX4 regulates human EGA by inducing cleavage-stage-specific genes, while it also induces cell death. We report here that a short-pulsed expression of DUX4 in primed hESCs activates an EGA-like gene expression program in up to 17% of the cells, retaining cell viability. These DUX4-induced cells resembled eight-cell stage blastomeres and were named induced blastomere-like (iBM) cells. The iBM cells showed marked reduction of POU5F1 protein, as previously observed in mouse two-cell-like cells. Finally, the iBM cells were successfully enriched using an antibody against NaPi2b (SLC34A2), which is expressed in human blastomeres. The iBM cells provide an improved model system to study human EGA transcriptome.
Subject: ZYGOTIC GENOME ACTIVATION
TRANSCRIPTION FACTORS
GENE
NAIVE
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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