Evidence map›Paper›PMID 40338744›Full record

ArticleCell reports2025

Proteogenomic reprogramming to a functional human blastomere-like stem cell state via a PARP-DUX4 regulatory axis.

Ludovic Zimmerlin, Ariana Angarita, Tea Soon Park, Rebecca Evans-Moses, Justin Thomas, Sirui Yan, Isabel Uribe, Isabella Vegas, Clara Kochendoerfer, Willem Buys and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Ludovic ZimmerlinInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Ariana AngaritaInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Tea Soon ParkInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Rebecca Evans-MosesInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Justin ThomasInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Sirui YanInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Isabel UribeDepartments of Biochemistry and Molecular Biology, The Johns Hopkins School of Public Health, Baltimore, MD, USA.
Isabella VegasInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Clara KochendoerferInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Willem BuysInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Anthony K L LeungDepartments of Biochemistry and Molecular Biology, The Johns Hopkins School of Public Health, Baltimore, MD, USA.
Elias T ZambidisInstitute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: ezambid1@jhmi.edu.

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI JEFFREY MUMM · 1985 to 2026
$22.1M
Embryonic vascular stem-progenitors for treatment of ischemic retinopathiesR01EY032113 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2021 to 2024
$2.0M
Pluripotent Stem Cell Vascular Therapies for Ischemic RetinopathiesR01EY023962 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2014 to 2018
$1.8M
Functional Vascular Progenitors from Naive Human iPSCR01HD082098 · NICHD · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2015 to 2019
$1.7M
The Chemistry-Biology Interface Program at Johns Hopkins UniversityT32GM149382 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI STEVEN E ROKITA · 2023 to 2026
$1.4M
Fourier Transform Orbitrap Fusion Lumos Tribrid Mass Spectrometer with ETDS10OD021844 · OD · JOHNS HOPKINS UNIVERSITY · PI PANDEY, AKHILESH · 2016 to 2016
$1.1M
Origin of HSC from Embryonic Stem CellsK08HL077595 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2004 to 2008
$666k
Transcriptional and Epigenetic Regulation of HSC Generated from iPS and ESCR03HL096220 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI FRIEDMAN, ALAN D, ZAMBIDIS, ELIAS T. · 2009 to 2009
$41k
NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY023962NEI NIH HHS R01 EY032113NHLBI NIH HHS K08 HL077595NHLBI NIH HHS R03 HL096220NICHD NIH HHS R01 HD082098NIGMS NIH HHS T32 GM149382NIH HHS S10 OD021844
6 · The paper itself

Abstract

Here, we show that conventional human pluripotent stem cells cultured with non-specific tankyrase-PARP1-inhibited conditions underwent proteogenomic reprogramming to functional blastomere-like tankyrase/PARP inhibitor-regulated naive stem cells (TIRN-SC). TIRN-SCs concurrently expressed hundreds of pioneer factors in hybrid 2C-8C-morula-ICM programs that were augmented by induced expression of DUX4. Injection of TIRN-SCs into 8C-staged murine embryos equipotently differentiated human cells to the extra-embryonic and embryonic compartments of chimeric blastocysts and fetuses. Ectopic expression of murine-E-Cadherin in TIRN-SCs further enhanced interspecific chimeric tissue targeting. TIRN-SC-derived trophoblast stem cells efficiently generated placental chimeras. Proteome-ubiquitinome analyses revealed increased TNKS and reduced PARP1 levels and an ADP-ribosylation-deficient, hyper-ubiquitinated proteome that impacted expression of both tankyrase and PARP1 substrates. ChIP-seq of NANOG-SOX2-OCT4 and PARP1 (NSOP) revealed genome-wide NSOP co-binding at DUX4-accessible enhancers of embryonic lineage factors; suggesting a DUX4-NSOP axis regulated TIRN-SC lineage plasticity. TIRN-SCs may serve as valuable models for studying the proteogenomic regulation of pre-lineage human embryogenesis. VIDEO ABSTRACT.

Indexed as

BlastomeresCellular ReprogrammingHomeodomain ProteinsPoly (ADP-Ribose) Polymerase-1AnimalsCell DifferentiationFemaleHumansMicePluripotent Stem CellsTankyrasesDUX4L1 protein, humanHomeodomain ProteinsPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1TankyrasesblastomerechimeraCP: Stem cell researchDUX4NANOGPARPproteometankyrasetotipotencyubiquitinationZGA

Identifiers

PMID40338744
PMCPMC12541798

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.