Nlrc3 signaling is indispensable for hematopoietic stem cell emergence via Notch signaling in vertebrates

Shuyang Cai, Honghu Li, Ruxiu Tie, Wei Shan, Qian Luo, Shufen Wang, Cong Feng, Huiqiao Chen, Meng Zhang, Yulin Xu, Xia Li, Ming Chen, Jiahui Lu (), Pengxu Qian () and He Huang ()
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Shuyang Cai: Zhejiang University School of Medicine
Honghu Li: Zhejiang University School of Medicine
Ruxiu Tie: Zhejiang University School of Medicine
Wei Shan: Zhejiang University School of Medicine
Qian Luo: Zhejiang University School of Medicine
Shufen Wang: Zhejiang University School of Medicine
Cong Feng: Zhejiang University
Huiqiao Chen: Zhejiang University School of Medicine
Meng Zhang: Zhejiang University School of Medicine
Yulin Xu: Zhejiang University School of Medicine
Xia Li: Zhejiang University School of Medicine
Ming Chen: Zhejiang University
Jiahui Lu: Shanghai University of Traditional Chinese Medicine
Pengxu Qian: Zhejiang University Medical Center
He Huang: Zhejiang University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Hematopoietic stem and progenitor cells generate all the lineages of blood cells throughout the lifespan of vertebrates. The emergence of hematopoietic stem and progenitor cells is finely tuned by a variety of signaling pathways. Previous studies have revealed the roles of pattern-recognition receptors such as Toll-like receptors and RIG-I-like receptors in hematopoiesis. In this study, we find that Nlrc3, a nucleotide-binding domain leucine-rich repeat containing family gene, is highly expressed in hematopoietic differentiation stages in vivo and vitro and is required in hematopoiesis in zebrafish. Mechanistically, nlrc3 activates the Notch pathway and the downstream gene of Notch hey1. Furthermore, NF-kB signaling acts upstream of nlrc3 to enhance its transcriptional activity. Finally, we find that Nlrc3 signaling is conserved in the regulation of murine embryonic hematopoiesis. Taken together, our findings uncover an indispensable role of Nlrc3 signaling in hematopoietic stem and progenitor cell emergence and provide insights into inflammation-related hematopoietic ontogeny and the in vitro expansion of hematopoietic stem and progenitor cells.

Date: 2024
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DOI: 10.1038/s41467-023-44251-6

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