Evidence map›Paper›PMID 42599997›Full record

ArticleScience advances2026

Genome folding and nuclear speckles converge to orchestrate fibroblast activation.

Zachary Gardner, Ricardo Linares-Saldana, Krishna Kumar Haridhasapavalan, Pedro O Méndez Fernández, Vasia Barka, Rachel Yang, Bailey Koch-Bojalad, Arun Padmanabhan, Qiaohong Wang, Parisha P Shah and 3 more

Abstract read
In one paragraph

Article in Science advances, 2026. 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

13 authors.

Zachary GardnerPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0003-1905-8686
Ricardo Linares-SaldanaPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0003-2657-825X
Krishna Kumar HaridhasapavalanPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0003-1610-0738
Pedro O Méndez FernándezPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0003-4159-9366
Vasia BarkaPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0009-0001-4281-8623
Rachel YangPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0002-8606-2565
Bailey Koch-BojaladPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Arun PadmanabhanGladstone Institutes, San Francisco, CA, USA.ORCID 0000-0002-6806-3046
Qiaohong WangPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0009-0005-6814-4195
Parisha P ShahPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0002-7756-6868
Son C NguyenPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0003-2187-1027
Eric F JoycePerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0002-0418-2804
Rajan JainPerelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0002-1979-044X

Funding

Training Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0M
Graduate Training in Developmental BiologyT32HD083185 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael Granato, Foteini Mourkioti · 2015 to 2026
$4.0M
Deciphering how 3D genome organization orchestrates cardiac cellular identityR35HL166663 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rajan Jain · 2023 to 2026
$3.5M
Predoctoral Training Program in GeneticsT32GM156697 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Montserrat C Anguera, DOUGLAS J EPSTEIN · 2025 to 2026
$1.1M
Padmanabhan K08 Admin SupplementK08HL157700 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PADMANABHAN, ARUN · 2021 to 2025
$830k
NHLBI NIH HHS K08 HL157700NHLBI NIH HHS R35 HL166663NHLBI NIH HHS T32 HL007843NICHD NIH HHS T32 HD083185NIGMS NIH HHS T32 GM156697
6 · The paper itself

Abstract

Fibroblasts adopt diverse cell states in response to inductive cues to maintain tissue homeostasis. We leveraged this cell-state plasticity to define how genome organization contributes to changes in cellular identity. We show that TGF-β reconfigures topologically associating domains and chromatin loops at genes upregulated during fibroblast activation into myofibroblasts. Cohesin is required for gene induction during fibroblast activation, and enhanced cohesin stability is sufficient to bypass TGF-β signaling and drive a myofibroblast-like state. Emerging evidence suggests chromatin spatial positioning relative to nuclear speckles can regulate gene expression. Therefore, we examined the role of the critical nuclear speckle component SON and showed that it is required for myofibroblast gene expression. Notably, enhancing genome folding partially rescued gene expression in fibroblasts with SON-depleted nuclear speckles. Together, these findings advance our understanding of fibrosis and support a model in which distinct facets of genome organization converge to orchestrate cell-state transitions.

Indexed as

Cell NucleusFibroblastsGenomeAnimalsCell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsGene Expression RegulationHumansMiceMyofibroblastsSignal TransductionTransforming Growth Factor betaCell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsTransforming Growth Factor beta

Identifiers

PMID42599997
PMCPMC13475600

What Socratic holds

Textmetadata
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.