Evidence map›Paper›PMID 38701778›Full record

ArticleStem cell reports2024

The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.

Shoma Nakagawa, Davide Carnevali, Xiangtian Tan, Mariano J Alvarez, David-Emlyn Parfitt, Umberto Di Vicino, Karthik Arumugam, William Shin, Sergi Aranda, Davide Normanno and 7 more

Abstract read
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Shoma NakagawaCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Davide CarnevaliCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Xiangtian TanDepartment of Systems Biology, Columbia University, New York, NY, USA.
Mariano J AlvarezDepartment of Systems Biology, Columbia University, New York, NY, USA; DarwinHealth Inc, New York, NY, USA.
David-Emlyn ParfittDepartments of Medicine, Genetics and Development, Urology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Umberto Di VicinoCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Karthik ArumugamCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
William ShinDepartment of Systems Biology, Columbia University, New York, NY, USA.
Sergi ArandaCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Davide NormannoCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; Institute of Human Genetics, CNRS, Montpellier, France.
Ruben Sebastian-PerezCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Chiara CannatáCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Paola CortesCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Maria Victoria NeguemborCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Michael M ShenDepartment of Systems Biology, Columbia University, New York, NY, USA; Departments of Medicine, Genetics and Development, Urology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Andrea CalifanoDepartment of Systems Biology, Columbia University, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA; Department of Biochemistry and Molecular Biophysics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Biomedical Informatics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Chan Zuckerberg Biohub New York, New York, NY, USA. Electronic address: ac2248@cumc.columbia.edu.
Maria Pia CosmaCenter for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; ICREA, Pg.Lluis Companys 23, 08010 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Er Road, Yuexiu District, Guangzhou 510080, China. Electronic address: pia.cosma@crg.es.

Funding

Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Analysis of epithelial heterogeneity in prostate development and cancerR01CA238005 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, MICHAEL M. · 2019 to 2023
$2.1M
High-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0M
High Performance Computing Cluster for Biomedical ResearchS10OD032433 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2023 to 2023
$2.0M
Systems analysis of mouse gastrulationR01HD085904 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, MICHAEL M. · 2016 to 2020
$1.7M
Storage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600k
NCI NIH HHS R01 CA238005NCI NIH HHS R35 CA197745NICHD NIH HHS R01 HD085904NIH HHS S10 OD012351NIH HHS S10 OD021764NIH HHS S10 OD032433
6 · The paper itself

Abstract

Embryo size, specification, and homeostasis are regulated by a complex gene regulatory and signaling network. Here we used gene expression signatures of Wnt-activated mouse embryonic stem cell (mESC) clones to reverse engineer an mESC regulatory network. We identify NKX1-2 as a novel master regulator of preimplantation embryo development. We find that Nkx1-2 inhibition reduces nascent RNA synthesis, downregulates genes controlling ribosome biogenesis, RNA translation, and transport, and induces severe alteration of nucleolus structure, resulting in the exclusion of RNA polymerase I from nucleoli. In turn, NKX1-2 loss of function leads to chromosome missegregation in the 2- to 4-cell embryo stages, severe decrease in blastomere numbers, alterations of tight junctions (TJs), and impairment of microlumen coarsening. Overall, these changes impair the blastocoel expansion-collapse cycle and embryo cavitation, leading to altered lineage specification and developmental arrest.

Indexed as

Embryonic DevelopmentGene Expression Regulation, DevelopmentalHomeodomain ProteinsTranscription FactorsAnimalsBlastocystCell NucleolusMiceMouse Embryonic Stem CellsNuclear ProteinsTight JunctionsWnt ProteinsWnt Signaling PathwayHomeodomain ProteinsNkx1-2 protein, mouseNuclear ProteinsTranscription FactorsWnt Proteinsembryonic stem cellmaster regulator analysismouse embryoNKX1-2nucleolusribosome biogenesisRNA polymerase Isystems biologyWnt signaling

Identifiers

PMID38701778
PMCPMC11103935

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.