Evidence map›Paper›PMID 41279640›Full record

ArticlebioRxiv : the preprint server for biology2025

MERFISH+, a large-scale, multi-omics spatial technology resolves the molecular holograms of the 3D human developing heart.

Colin Kern, Qingquan Zhang, Yifan Lu, Jacqueline Eschbach, Zehua Zeng, Elie N Farah, Chu-Yi Tai, Kaifu Yang, Ignatius Jenie, Fenyong Yao and 14 more

Abstract readPreprint
PubMed Full text at PMC Publisher
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

24 authors.

Colin KernDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-3249-6405
Qingquan ZhangDepartment of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-2153-6491
Yifan LuDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3787-0440
Jacqueline EschbachDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0009-0000-5000-2782
Zehua ZengDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0002-2109-0418
Elie N FarahDepartment of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-2412-0950
Chu-Yi TaiDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Kaifu YangDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Ignatius JenieDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0009-0009-2849-1116
Fenyong YaoDepartment of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.
Zoey ZhaoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0009-0005-3822-7985
Qixuan MaDepartment of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.
Carlos Garcia PadillaDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Alexander MonellDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-5399-2205
Siavash MoghadamiDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-1251-7384
Fugui ZhuDepartment of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.
Bin LiDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Angie HouDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Grant TuckerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
David EllisonInfrastructure Solution Group, Lenovo.
Neil C ChiDepartment of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-2324-3796
Xiaojie QiuDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0002-7881-5395
Quan ZhuDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-5731-4658
Bogdan BintuDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0001-9096-5858

Funding

High-throughput imaging of 3D chromatin regulation events in the nervous systemDP5OD031878 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BINTU, BOGDAN · 2021 to 2025
$2.0M
REQUEST OF MERSCOPE FOR SPATIAL TRANSCRIPTOMICSS10OD032391 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHU, QUAN · 2022 to 2022
$333k
NIH HHS DP5 OD031878NIH HHS S10 OD032391
6 · The paper itself

Abstract

Hybridization-based spatial transcriptomics technologies have advanced our ability to map cellular and subcellular organization in complex tissues. However, existing methods remain constrained in gene coverage, multimodal compatibility, and scalability. Here, we present MERFISH+, an enhanced version of Multiplexed Error-Robust Fluorescence in Situ Hybridization (MERFISH), which integrates chemical probe anchoring in protective hydrogels with high-throughput microfluidics and microscopy. This optimized design supports robust and repeated hybridization cycles across an entire centimeter-scale tissue sample. MERFISH+ allowed to simultaneously quantify over 1,800 genes and resolve the 3D organization of chromatin loci and their associated epigenomic marks in developing human hearts. Using a generative integration framework for spatial multimodal data (Spateo-VI), we harmonized these MERFISH+ transcriptomic and chromatin data to reconstruct a 3D spatially-resolved multi-omic atlas of the developing human heart at subcellular resolution capturing 3.1 million cells across 34 distinct populations. This 3D atlas provides a holistic view of an entire organ enabling the characterization of 3D cellular neighborhoods and transcriptional gradients of substructures such as the descending arteries. Thus, MERFISH+ offers a robust, large-format platform for spatial multi-omics that enables high resolution mapping of gene expression at subcellular resolution and the characterization of cellular organization within 3D organs.

Identifiers

PMID41279640
PMCPMC12637541

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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.