Pluripotent stem cells with low differentiation potential contain incompletely reprogrammed DNA replication.

The Journal of Cell Biology
Theodore PanizaJeannine Gerhardt

Abstract

Reprogrammed pluripotent stem cells (PSCs) are valuable for research and potentially for cell replacement therapy. However, only a fraction of reprogrammed PSCs are developmentally competent. Genomic stability and accurate DNA synthesis are fundamental for cell development and critical for safety. We analyzed whether defects in DNA replication contribute to genomic instability and the diverse differentiation potentials of reprogrammed PSCs. Using a unique single-molecule approach, we visualized DNA replication in isogenic PSCs generated by different reprogramming approaches, either somatic cell nuclear transfer (NT-hESCs) or with defined factors (iPSCs). In PSCs with lower differentiation potential, DNA replication was incompletely reprogrammed, and genomic instability increased during replicative stress. Reprogramming of DNA replication did not correlate with DNA methylation. Instead, fewer replication origins and a higher frequency of DNA breaks in PSCs with incompletely reprogrammed DNA replication were found. Given the impact of error-free DNA synthesis on the genomic integrity and differentiation proficiency of PSCs, analyzing DNA replication may be a useful quality control tool.

References

Sep 12, 2000·Molecular Biology of the Cell·N C KappasJ C Sible
Sep 14, 2001·Human Molecular Genetics·M M SantosM Pandolfo
Aug 13, 2002·Cancer Biology & Therapy·Jennifer L Bandura, Brian R Calvi
Aug 20, 2003·The Journal of Clinical Investigation·Michael RistowAndreas F H Pfeiffer
Jan 30, 2008·Nature Reviews. Genetics·Andrés Aguilera, Belén Gómez-González
Jul 5, 2008·Nature Protocols·In-Hyun ParkGeorge Q Daley
Aug 30, 2008·Nature Reviews. Cancer·J Julian Blow, Peter J Gillespie
Aug 13, 2009·Nature·Michael J BolandKristin K Baldwin
Sep 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·René MaehrDouglas A Melton
Feb 24, 2010·Nature Reviews. Molecular Cell Biology·Dana Branzei, Marco Foiani
Jul 21, 2010·Nature·K KimG Q Daley
Aug 5, 2010·Cell Stem Cell·Aaron M Newman, James B Cooper
Dec 22, 2010·The Journal of Cell Biology·Xin Quan Ge, J Julian Blow
Jun 4, 2011·PLoS Genetics·Koichiro NishinoAkihiro Umezawa
Oct 27, 2011·PLoS Computational Biology·Tyrone RybaDavid M Gilbert
Mar 12, 2013·Cell Stem Cell·Sayaka WakayamaTeruhiko Wakayama
May 21, 2013·Cell·Masahito TachibanaShoukhrat Mitalipov
Nov 12, 2013·Molecular Cell·Siem van der LaanDomenico Maiorano
Dec 3, 2013·Molecular Cell·Jeannine GerhardtCarl L Schildkraut
Sep 3, 2014·The Journal of Cell Biology·Jeannine GerhardtCarl L Schildkraut
Nov 19, 2014·International Journal of Molecular Sciences·Saranya P WylesTimothy J Nelson
Jun 2, 2015·Nature·Matthew D SchultzJoseph R Ecker
Oct 27, 2015·Nature Biotechnology·Jiho ChoiKonrad Hochedlinger
Jan 21, 2017·Genes·Chames KermiDomenico Maiorano
Mar 16, 2017·The New England Journal of Medicine·Michiko MandaiMasayo Takahashi

❮ Previous
Next ❯

Citations

Aug 29, 2020·The Journal of Cell Biology·Brandon L MoueryJeanette Gowen Cook
Aug 30, 2021·Current Opinion in Genetics & Development·Yea-Lih Lin, Philippe Pasero

❮ Previous
Next ❯

Methods Mentioned

BETA
Flow cytometry
fluorescence microscopy
electrophoresis
PCR

Software Mentioned

IPlab
methylpy
SMARD

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.