Evidence map›Paper›PMID 41344326›Full record

ArticleCell2025

Fertilization triggers early proteomic symmetry breaking in mammalian embryos.

Lisa K Iwamoto-Stohl, Aleksandra A Petelski, Baiyi Quan, Maciej Meglicki, Audrey Fu, Shoma Nakagawa, Breanna McMahon, Ting-Yu Wang, Saad Khan, Harrison Specht and 12 more

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Subcellularly Resolved 3D Translatome in Mouse Oocytes and Early Embryos.bioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Review
  7. Probing RNA-protein interactions in the early mouse embryo.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Lisa K Iwamoto-StohlDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; Division of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Aleksandra A PetelskiDepartment of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA; Parallel Squared Technology Institute, Watertown, MA 02472, USA.
Baiyi QuanDivision of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Maciej MeglickiDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Audrey FuDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Shoma NakagawaDivision of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Breanna McMahonDivision of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Ting-Yu WangDivision of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Saad KhanDepartment of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA.
Harrison SpechtDepartment of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA; Parallel Squared Technology Institute, Watertown, MA 02472, USA.
Gray HuffmanDepartment of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA.
Jason DerksDepartment of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA; Parallel Squared Technology Institute, Watertown, MA 02472, USA.
Sergi JunyentDivision of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA.
Bailey A T WeatherbeeDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Antonia WeberlingDepartment of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge CB2 1QW, UK.
Carlos W GantnerDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Rachel S MandelbaumDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
Richard J PaulsonDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
Lisa LamDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
Tsui-Fen ChouDivision of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA. Electronic address: tfchou@caltech.edu.
Nikolai SlavovDepartment of Bioengineering and Barnett Institute, Northeastern University, Boston, MA 02115, USA; Parallel Squared Technology Institute, Watertown, MA 02472, USA. Electronic address: nslavov@northeastern.edu.
Magdalena Zernicka-GoetzDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; Division of Biology and Biological Engineering, California Institute of Technology (Caltech), Pasadena, CA 91125, USA. Electronic address: magdaz@caltech.edu.

Funding

Temporal program for cell fate specification in the mouse embryoR01HD100456 · NICHD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Magdalena Zernicka-Goetz · 2020 to 2026
$3.3M
Biological mechanisms that eliminate aneuploid cells from a mosaic conceptus in the mouse model systemR01HD101489 · NICHD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI ZERNICKA-GOETZ, MAGDALENA · 2021 to 2025
$2.6M
Ribosome-mediated translational regulation during stem cell differentiationDP2GM123497 · NIGMS · NORTHEASTERN UNIVERSITY · PI SLAVOV, NIKOLAI · 2016 to 2016
$2.4M
Molecular and metabolic influences on the activation of monocytes and macrophages at single-cell resolutionR35GM148218 · NIGMS · NORTHEASTERN UNIVERSITY · PI Nikolai Slavov · 2023 to 2026
$1.5M
Collaborative Research: DMS/NIGMS 2: Methods for Systematic Analysis of Post-transcriptional Regulation in Single CellsR01GM144967 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI FRANKS, ALEXANDER, SLAVOV, NIKOLAI · 2021 to 2024
$779k
NICHD NIH HHS R01 HD100456NICHD NIH HHS R01 HD101489NIGMS NIH HHS DP2 GM123497NIGMS NIH HHS R01 GM144967NIGMS NIH HHS R35 GM148218Wellcome Trust
6 · The paper itself

Abstract

While non-mammalian embryos often rely on spatial pre-patterning, mammalian development has long been thought to begin with equivalent blastomeres. However, emerging evidence challenges this. Here, using multiplexed and label-free single-cell proteomics, we identify over 300 asymmetrically abundant proteins-many involved in protein degradation and transport-dividing mouse 2-cell-stage blastomeres into two distinct clusters, which we term alpha and beta. These proteomic asymmetries are detectable as early as the zygote stage, intensify by the 4-cell stage, and correlate with the sperm entry site, implicating fertilization as a symmetry-breaking event. Splitting 2-cell-stage embryos into halves reveals that beta blastomeres possess greater developmental potential than alpha blastomeres. Similar clustering and protein enrichment patterns found in human 2-cell embryos suggest this early asymmetry might be conserved. These findings uncover a previously unrecognized proteomic pre-patterning triggered by fertilization in mammalian embryos, with important implications for understanding totipotency and early lineage bias.

Indexed as

BlastomeresEmbryo, MammalianFertilizationProteomeAnimalsBody PatterningEmbryonic DevelopmentFemaleHumansMaleMiceProteomicsZygoteProteome2-cell blastomere asymmetriesdevelopmental biologyembryonic patterningepiblasthuman developmentlineage specificationmammalian embryonic developmentpre-implantation developmentsingle-cell proteomics by mass spectrometrytotipotency

Identifiers

PMID41344326
PMCPMC12712633

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.