Evidence map›Paper›PMID 34131144›Full record

ArticleNature communications2021

Integrated analysis of Xist upregulation and X-chromosome inactivation with single-cell and single-allele resolution.

Guido Pacini, Ilona Dunkel, Norbert Mages, Verena Mutzel, Bernd Timmermann, Annalisa Marsico, Edda G Schulz

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.0field-weighted citation impact, top 7% of its field
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

29 citing papers in PubMed, 54 citations in OpenAlex.

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  9. ASPEN: Robust detection of allelic dynamics in single cell RNA-seq.bioRxiv : the preprint server for biology · 2025
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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

7 authors at 2 institutions in 1 country.

Guido PaciniOtto Warburg Laboratories, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Ilona DunkelOtto Warburg Laboratories, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Norbert MagesSequencing core facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Verena MutzelOtto Warburg Laboratories, Max Planck Institute for Molecular Genetics, Berlin, Germany.ORCID 0000-0001-7237-0324
Bernd TimmermannSequencing core facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Annalisa Marsico *Institute for Computational Biology, Helmholtz Center, München, Germany. annalisa.marsico@helmholtz-muenchen.de.ORCID 0000-0003-0327-5555
Edda G Schulz *Otto Warburg Laboratories, Max Planck Institute for Molecular Genetics, Berlin, Germany. edda.schulz@molgen.mpg.de.ORCID 0000-0003-1253-6868
Max Planck Institute for Molecular Genetics · DEHelmholtz Zentrum München · DE

Funding

BIOBEHAVIORAL STUDIES OF NARCOTICS ABUSE IN HUMANSK05DA000064 · NIDA · MC LEAN HOSPITAL (BELMONT, MA) · PI MENDELSON, JACK H · 1985 to 2007
$911k
NIDA NIH HHS K05 DA000064
6 · The paper itself

Abstract

To ensure dosage compensation between the sexes, one randomly chosen X chromosome is silenced in each female cell in the process of X-chromosome inactivation (XCI). XCI is initiated during early development through upregulation of the long non-coding RNA Xist, which mediates chromosome-wide gene silencing. Cell differentiation, Xist upregulation and gene silencing are thought to be coupled at multiple levels to ensure inactivation of exactly one out of two X chromosomes. Here we perform an integrated analysis of all three processes through allele-specific single-cell RNA-sequencing. Specifically, we assess the onset of random XCI in differentiating mouse embryonic stem cells, and develop dedicated analysis approaches. By exploiting the inter-cellular heterogeneity of XCI onset, we identify putative Xist regulators. Moreover, we show that transient Xist upregulation from both X chromosomes results in biallelic gene silencing right before transitioning to the monoallelic state, confirming a prediction of the stochastic model of XCI. Finally, we show that genetic variation modulates the XCI process at multiple levels, providing a potential explanation for the long-known X-controlling element (Xce) effect, which leads to preferential inactivation of a specific X chromosome in inter-strain crosses. We thus draw a detailed picture of the different levels of regulation that govern the initiation of XCI. The experimental and computational strategies we have developed here will allow us to profile random XCI in more physiological contexts, including primary human cells in vivo.

Indexed as

Up-RegulationX Chromosome InactivationAllelesAnimalsDosage Compensation, GeneticFemaleGene SilencingMiceMice, Inbred C57BLMouse Embryonic Stem CellsRNA, Long NoncodingSequence Analysis, RNAX ChromosomeRNA, Long NoncodingXIST non-coding RNA

Identifiers

PMID34131144
PMCPMC8206119
OpenAlexW3169771247

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.