Evidence map›Paper›PMID 40551012›Full record

ArticleThe EMBO journal2025

Epiblast-derived CX3CR1+ progenitors generate cardiovascular cells during cardiogenesis.

Kyuwon Cho, Mark Andrade, Saeed Khodayari, Christine Lee, Seongho Bae, Sangsung Kim, Jin Eyun Kim, Young-Sup Yoon

Erratum issuedAbstract read
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Review
  2. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Kyuwon ChoDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Mark AndradeDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.ORCID http://orcid.org/0000-0002-5194-578X
Saeed KhodayariDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Christine LeeDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.ORCID http://orcid.org/0009-0008-5097-7318
Seongho BaeDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.ORCID http://orcid.org/0000-0002-3624-6649
Sangsung KimSeverance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jin Eyun KimDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Young-Sup YoonDepartment of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA. yyoon5@emory.edu.ORCID http://orcid.org/0000-0003-0051-0935

Funding

Vascular Regeneration with Direct Reprogramming and Engineering StrategiesR01HL157242 · NHLBI · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2022 to 2025
$2.1M
Lymphatic Regeneration by Direct Cellular ReprogrammingR01HL166817 · NHLBI · EMORY UNIVERSITY · PI Sang-Ho Lee, Young-Sup Yoon · 2023 to 2026
$2.1M
Vascular Regeneration with Human Pluripotent Stem Cell-derived Vascular Cells and Engineering ApproachesR01HL156008 · NHLBI · EMORY UNIVERSITY · PI YOON, YOUNG-SUP · 2022 to 2025
$2.0M
American Heart Association (AHA) 916760HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL156008HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL157242HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL166817NHLBI NIH HHS R01 HL156008NHLBI NIH HHS R01 HL157242NHLBI NIH HHS R01 HL166817
6 · The paper itself

Abstract

CX3CR1+ cells generate tissue macrophages in the developing heart and play cardioprotective roles in response to ischemic injuries in the adult heart. However, the origin and fate of CX3CR1+ cells during cardiogenesis remain unclear. Here, we performed genetic lineage tracing of CX3CR1+ cells and their progeny (termed Cx3cr1 lineage cells) in the mouse and demonstrated that they emerge from a subset of epiblast cells at embryonic day E6.5 and contribute to the parietal endoderm cells at E7.0. At E8.0-9.5 of development, Cx3cr1 lineage cells produced cardiomyocytes and endothelial cells via both de novo differentiation and fusion with pre-existing cardiomyocytes or endothelial cells, respectively. Cx3cr1 lineage cells persisted in the adult heart, comprising ~13% of cardiomyocytes and ~31% of endothelial cells. Additionally, CX3CR1+ cells differentiated from mouse embryonic stem cells generated cardiomyocytes, endothelial cells, and macrophages in vitro, ex vivo, and in vivo. Single-cell RNA sequencing revealed that Cx3cr1+ cells represent an intermediate cell population transitioning from embryonic stem cells to mesoderm. Taken together, embryonic CX3CR1+ cells constitute a multipotent epiblast-derived progenitor population that contributes not only to the formation of macrophages, but also of cardiomyocytes and endothelial cells.

Indexed as

CX3C Chemokine Receptor 1Germ LayersHeartMyocytes, CardiacOrganogenesisAnimalsCell DifferentiationCell LineageEmbryonic Stem CellsEndothelial CellsMacrophagesMiceMouse Embryonic Stem CellsCX3C Chemokine Receptor 1Cx3cr1 protein, mouseCardiogenesisCardiomyocyteCX3CR1Endothelial CellsGenetic Lineage Tracing

Identifiers

PMID40551012
PMCPMC12316875

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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.