Evidence map›Paper›PMID 27486082›Full record

ArticleGenome research2016

Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation.

Geng Chen, John Paul Schell, Julio Aguila Benitez, Sophie Petropoulos, Marlene Yilmaz, Björn Reinius, Zhanna Alekseenko, Leming Shi, Eva Hedlund, Fredrik Lanner and 2 more

Abstract read
In one paragraph

Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing 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

63 citing papers in PubMed.

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3 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

12 authors.

Geng ChenDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; School of Pharmacy, Fudan University, 201203 Shanghai, China.
John Paul SchellDepartment of Clinical Science, Intervention and Technology and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.
Julio Aguila BenitezDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Sophie PetropoulosDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Clinical Science, Intervention and Technology and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.
Marlene YilmazDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Björn ReiniusDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Zhanna AlekseenkoDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Leming ShiSchool of Pharmacy, Fudan University, 201203 Shanghai, China.
Eva HedlundDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Fredrik LannerDepartment of Clinical Science, Intervention and Technology and Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.
Rickard SandbergDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Ludwig Institute for Cancer Research, 171 77 Stockholm, Sweden.
Qiaolin DengDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we "digitalized" XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.

Indexed as

Cell DifferentiationX Chromosome InactivationAnimalsCells, CulturedEmbryonic Stem CellsFemaleGene Expression Regulation, DevelopmentalMaleMiceMice, Inbred C57BLPluripotent Stem CellsSingle-Cell AnalysisTranscriptome

Identifiers

PMID27486082
PMCPMC5052059

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Registered trials

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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.