Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation

Abstract Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte–macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore...

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Main Authors: Yuya Suzuki, Takuo Emoto, Shunsuke Sato, Takeshi Yoshida, Mitsuhiko Shoda, Hiromi Endoh, Manabu Nagao, Tomoyo Hamana, Taishi Inoue, Tomohiro Hayashi, Eriko Nitta, Hiroki Konishi, Kunihiko Kiuchi, Mitsuru Takami, Kimitake Imamura, Masayuki Taniguchi, Masatoshi Inoue, Toshihiro Nakamura, Yusuke Sonoda, Hiroyuki Takahara, Kazutaka Nakasone, Kyoko Yamamoto, Kenichi Tani, Hidehiro Iwai, Yusuke Nakanishi, Shogo Yonehara, Atsushi Murakami, Ryuji Toh, Takenao Ohkawa, Tomoyuki Furuyashiki, Ryo Nitta, Tomoya Yamashita, Ken-ichi Hirata, Koji Fukuzawa
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07308-w
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author Yuya Suzuki
Takuo Emoto
Shunsuke Sato
Takeshi Yoshida
Mitsuhiko Shoda
Hiromi Endoh
Manabu Nagao
Tomoyo Hamana
Taishi Inoue
Tomohiro Hayashi
Eriko Nitta
Hiroki Konishi
Kunihiko Kiuchi
Mitsuru Takami
Kimitake Imamura
Masayuki Taniguchi
Masatoshi Inoue
Toshihiro Nakamura
Yusuke Sonoda
Hiroyuki Takahara
Kazutaka Nakasone
Kyoko Yamamoto
Kenichi Tani
Hidehiro Iwai
Yusuke Nakanishi
Shogo Yonehara
Atsushi Murakami
Ryuji Toh
Takenao Ohkawa
Tomoyuki Furuyashiki
Ryo Nitta
Tomoya Yamashita
Ken-ichi Hirata
Koji Fukuzawa
author_facet Yuya Suzuki
Takuo Emoto
Shunsuke Sato
Takeshi Yoshida
Mitsuhiko Shoda
Hiromi Endoh
Manabu Nagao
Tomoyo Hamana
Taishi Inoue
Tomohiro Hayashi
Eriko Nitta
Hiroki Konishi
Kunihiko Kiuchi
Mitsuru Takami
Kimitake Imamura
Masayuki Taniguchi
Masatoshi Inoue
Toshihiro Nakamura
Yusuke Sonoda
Hiroyuki Takahara
Kazutaka Nakasone
Kyoko Yamamoto
Kenichi Tani
Hidehiro Iwai
Yusuke Nakanishi
Shogo Yonehara
Atsushi Murakami
Ryuji Toh
Takenao Ohkawa
Tomoyuki Furuyashiki
Ryo Nitta
Tomoya Yamashita
Ken-ichi Hirata
Koji Fukuzawa
author_sort Yuya Suzuki
collection DOAJ
description Abstract Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte–macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq. Myeloid cells in LA tissue are categorized into five macrophage clusters, three monocyte clusters, and others. Cell-Chat analysis revealed that monocytes and IL1B+ macrophages send epidermal growth factor (EGF) signals to fibroblasts. Amphiregulin (AREG) is the most upregulated gene in monocytes and IL1B+ macrophages in the AF group, compared with healthy controls from other groups. Serum AREG levels are higher in patients with persistent AF. These data suggested that EGF signaling pathway could be a therapeutic target for AF and serum AREG levels provide an effective biomarker for predicting persistent AF.
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spelling doaj-art-1d327f1dccc44eafa7b0fc74dd5430912025-08-20T02:00:13ZengNature PortfolioCommunications Biology2399-36422024-12-017111310.1038/s42003-024-07308-wLeft atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillationYuya Suzuki0Takuo Emoto1Shunsuke Sato2Takeshi Yoshida3Mitsuhiko Shoda4Hiromi Endoh5Manabu Nagao6Tomoyo Hamana7Taishi Inoue8Tomohiro Hayashi9Eriko Nitta10Hiroki Konishi11Kunihiko Kiuchi12Mitsuru Takami13Kimitake Imamura14Masayuki Taniguchi15Masatoshi Inoue16Toshihiro Nakamura17Yusuke Sonoda18Hiroyuki Takahara19Kazutaka Nakasone20Kyoko Yamamoto21Kenichi Tani22Hidehiro Iwai23Yusuke Nakanishi24Shogo Yonehara25Atsushi Murakami26Ryuji Toh27Takenao Ohkawa28Tomoyuki Furuyashiki29Ryo Nitta30Tomoya Yamashita31Ken-ichi Hirata32Koji Fukuzawa33Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Surgery, Department of Surgery, Yodogawa Christian HospitalDepartment of Information and Intelligence Engineering, Kobe UniversityDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of MedicineDivision of Evidence-Based Laboratory Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Yodogawa Christian HospitalDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Pharmacology, Kobe University Graduate School of MedicineDepartment of Information and Intelligence Engineering, Kobe UniversityDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Evidence-Based Laboratory Medicine, Kobe University Graduate School of MedicineDepartment of Information and Intelligence Engineering, Kobe UniversityDivision of Pharmacology, Kobe University Graduate School of MedicineDivision of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of MedicineAbstract Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte–macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq. Myeloid cells in LA tissue are categorized into five macrophage clusters, three monocyte clusters, and others. Cell-Chat analysis revealed that monocytes and IL1B+ macrophages send epidermal growth factor (EGF) signals to fibroblasts. Amphiregulin (AREG) is the most upregulated gene in monocytes and IL1B+ macrophages in the AF group, compared with healthy controls from other groups. Serum AREG levels are higher in patients with persistent AF. These data suggested that EGF signaling pathway could be a therapeutic target for AF and serum AREG levels provide an effective biomarker for predicting persistent AF.https://doi.org/10.1038/s42003-024-07308-w
spellingShingle Yuya Suzuki
Takuo Emoto
Shunsuke Sato
Takeshi Yoshida
Mitsuhiko Shoda
Hiromi Endoh
Manabu Nagao
Tomoyo Hamana
Taishi Inoue
Tomohiro Hayashi
Eriko Nitta
Hiroki Konishi
Kunihiko Kiuchi
Mitsuru Takami
Kimitake Imamura
Masayuki Taniguchi
Masatoshi Inoue
Toshihiro Nakamura
Yusuke Sonoda
Hiroyuki Takahara
Kazutaka Nakasone
Kyoko Yamamoto
Kenichi Tani
Hidehiro Iwai
Yusuke Nakanishi
Shogo Yonehara
Atsushi Murakami
Ryuji Toh
Takenao Ohkawa
Tomoyuki Furuyashiki
Ryo Nitta
Tomoya Yamashita
Ken-ichi Hirata
Koji Fukuzawa
Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
Communications Biology
title Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
title_full Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
title_fullStr Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
title_full_unstemmed Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
title_short Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
title_sort left atrial single cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation
url https://doi.org/10.1038/s42003-024-07308-w
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