Evidence map›Paper›PMID 26055160›Full record

ArticleGenome research2015

Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells.

Juan Carlos Rivera-Mulia, Quinton Buckley, Takayo Sasaki, Jared Zimmerman, Ruth A Didier, Kristopher Nazor, Jeanne F Loring, Zheng Lian, Sherman Weissman, Allan J Robins and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 184 citations in OpenAlex.

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  9. PARTAGE: Parallel analysis of replication timing and gene expression.bioRxiv : the preprint server for biology · 2025
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49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 1 country.

Juan Carlos Rivera-MuliaDepartment of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA;
Quinton BuckleyDepartment of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA;
Takayo SasakiDepartment of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA;
Jared ZimmermanDepartment of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA;
Ruth A DidierCollege of Medicine, Florida State University, Tallahassee, Florida 32306-4295, USA;
Kristopher NazorCenter for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA;
Jeanne F LoringCenter for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA;
Zheng LianDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut 06519, USA;
Sherman WeissmanDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut 06519, USA;
Allan J RobinsViaCyte, Inc., Athens, Georgia 30602, USA;
Thomas C SchulzViaCyte, Inc., Athens, Georgia 30602, USA;
Laura MenendezDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA;
Michael J KulikDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA;
Stephen DaltonDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA;
Haitham GabrDepartment of Computer and Information Sciences and Engineering, University of Florida, Gainesville, Florida 32611, USA;
Tamer KahveciDepartment of Computer and Information Sciences and Engineering, University of Florida, Gainesville, Florida 32611, USA;
David M GilbertDepartment of Biological Science, Florida State University, Tallahassee, Florida 32306-4295, USA; Center for Genomics and Personalized Medicine, Florida State University, Tallahassee, Florida 32306, USA.
Florida State University · USUniversity of Georgia · USScripps Research Institute · USUniversity of Florida · USViaCyte (United States) · USYale University · US

Funding

UNDERSTANDING MECHANISMS OF hESC SELF-RENEWAL AND CELL FATE COMMITMENTP01GM085354 · NIGMS · UNIVERSITY OF GEORGIA · PI DALTON, STEPHEN · 2008 to 2018
$18.3M
Genome Plasticity during ES Cell Differentiation to Neural LineagesR01GM083337 · NIGMS · SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE · PI David M Gilbert · 2007 to 2026
$6.1M
NIGMS NIH HHS GM083337NIGMS NIH HHS GM085354NIGMS NIH HHS P01 GM085354NIGMS NIH HHS R01 GM083337
6 · The paper itself

Abstract

Duplication of the genome in mammalian cells occurs in a defined temporal order referred to as its replication-timing (RT) program. RT changes dynamically during development, regulated in units of 400-800 kb referred to as replication domains (RDs). Changes in RT are generally coordinated with transcriptional competence and changes in subnuclear position. We generated genome-wide RT profiles for 26 distinct human cell types, including embryonic stem cell (hESC)-derived, primary cells and established cell lines representing intermediate stages of endoderm, mesoderm, ectoderm, and neural crest (NC) development. We identified clusters of RDs that replicate at unique times in each stage (RT signatures) and confirmed global consolidation of the genome into larger synchronously replicating segments during differentiation. Surprisingly, transcriptome data revealed that the well-accepted correlation between early replication and transcriptional activity was restricted to RT-constitutive genes, whereas two-thirds of the genes that switched RT during differentiation were strongly expressed when late replicating in one or more cell types. Closer inspection revealed that transcription of this class of genes was frequently restricted to the lineage in which the RT switch occurred, but was induced prior to a late-to-early RT switch and/or down-regulated after an early-to-late RT switch. Analysis of transcriptional regulatory networks showed that this class of genes contains strong regulators of genes that were only expressed when early replicating. These results provide intriguing new insight into the complex relationship between transcription and RT regulation during human development.

Indexed as

Cell LineageDNA Replication TimingCell DifferentiationCells, CulturedCluster AnalysisGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Regulatory NetworksGenome, HumanHumansPluripotent Stem Cells

Identifiers

PMID26055160
PMCPMC4509994
OpenAlexW2137279138

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.