Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5

Norika Liu, Naofumi Kawahira, Yasuhiro Nakashima, Haruko Nakano, Akiyasu Iwase, Yasunobu Uchijima, Mei Wang, Sean M. Wu, Susumu Minamisawa, Hiroki Kurihara and Atsushi Nakano ()
Additional contact information
Norika Liu: The Jikei University School of Medicine, Department of Cell Physiology
Naofumi Kawahira: University of California Los Angeles, Department of Molecular Cell and Developmental Biology
Yasuhiro Nakashima: Kyoto University, Department of Cardiovascular Medicine
Haruko Nakano: University of California Los Angeles, Department of Molecular Cell and Developmental Biology
Akiyasu Iwase: University of Tokyo, Department of Physiological Chemistry and Metabolism
Yasunobu Uchijima: University of Tokyo, Department of Physiological Chemistry and Metabolism
Mei Wang: The Jikei University School of Medicine, Department of Cell Physiology
Sean M. Wu: Stanford University, Cardiovascular Institute and Division of Cardiovascular Medicine, Department of Medicine
Susumu Minamisawa: The Jikei University School of Medicine, Department of Cell Physiology
Hiroki Kurihara: University of Tokyo, Department of Physiological Chemistry and Metabolism
Atsushi Nakano: The Jikei University School of Medicine, Department of Cell Physiology

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis. Signal network analysis from scRNA-seq datasets revealed that genes in Notch and retinoic acid (RA) signaling are significantly downregulated in Nkx2-5-null endocardial cells. In vivo and ex vivo analyses validate that the Nkx2-5-Notch axis is essential for the generation of both hemogenic and cushion endocardial cells, and the suppression of RA signaling via Dhrs3 expression plays important roles in further differentiation into macrophages. Genetic ablation study revealed that these macrophages are essential in cardiac valve remodeling. In summary, the study demonstrates that the Nkx2-5/Notch/RA signaling plays a pivotal role in macrophage differentiation from hematopoietic progenitors.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41039-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41039-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41039-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().