Evidence map›Paper›PMID 40791385›Full record

ArticlebioRxiv : the preprint server for biology2025

Gastruloid patterning reflects division of labor among biased stem cell clones.

Vinay Ayyappan, Catherine G Triandafillou, Kavitha Sarma, Arjun Raj

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

4 authors.

Vinay AyyappanDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Catherine G TriandafillouDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Kavitha SarmaThe Wistar Institute, Gene Expression and Regulation Program, Philadelphia, PA, USA.
Arjun RajDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Aaron Robert Goldman · 1985 to 2026
$75.9M
Engineering and Imaging 3D genome structure-function dynamics across time scalesU01DK127405 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BLOBEL, GERD A, PHILLIPS-CREMINS, JENNIFER ELIZABETH · 2020 to 2024
$5.7M
Decoding the bridges and barriers to cellular reprogramming and lineage identityR01GM137425 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN, RAJ, ARJUN · 2019 to 2023
$5.6M
An integrated approach to melanoma metastasis and therapy resistance: effects of age-related changes in the ECM and the biomechanics of the skinR01CA232256 · NCI · WISTAR INSTITUTE · PI CUKIERMAN, EDNA, RAJ, ARJUN · 2019 to 2023
$3.0M
Understanding and Overcoming Resistance to BRAF/MEK Kinase Inhibitors in MelanomaR01CA238237 · NCI · UNIVERSITY OF PENNSYLVANIA · PI HERLYN, MEENHARD F, RAJ, ARJUN · 2020 to 2024
$2.9M
NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA232256NCI NIH HHS R01 CA238237NIDDK NIH HHS U01 DK127405NIGMS NIH HHS R01 GM137425
6 · The paper itself

Abstract

Embryonic development typically requires precise coordination among cells to achieve reproducible outcomes, leading to the assumption that cellular heterogeneity must be minimized or buffered against. Using fluorescence-based lineage tracing in combination with spatial transcriptomics, we show that, in the gastruloid model of early development, pre-existing heterogeneity promotes proper axial organization through division of labor among stem cell clones. Individual clones isolated from a common population exhibit consistent spatial propensities for anterior or posterior fates. While pure clones generate elongated structures less frequently than a polyclonal population, mixing clones restores proper axial elongation. Spatial transcriptomics reveals that pure clones show disrupted gene expression with inappropriate coexpression of anterior and posterior markers, while clone combinations restore proper spatial organization. Using RNA-seq, ATAC-seq, and perturbations to key developmental signaling pathways, we further profile differences among clones and suggest a model whereby developmental precision emerges from the coordinated action of intrinsically biased clonal populations.

Identifiers

PMID40791385
PMCPMC12338665

What OpenQuestion holds

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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.