2. Academic Validation
  3. Rapid conversion of porcine pluripotent stem cells into macrophages with chemically defined conditions

Rapid conversion of porcine pluripotent stem cells into macrophages with chemically defined conditions

  • J Biol Chem. 2023 Dec 12:105556. doi: 10.1016/j.jbc.2023.105556.
Xiaolong Wu 1,  Yu Ni 2,  Wenhao Li 1,  Bin Yang 1,  Xinchun Yang 1,  Zhenshuo Zhu 1,  Juqing Zhang 1,  Xiaojie Wu 1,  Qiaoyan Shen 1,  Zheng Liao 1,  Liming Yuan 1,  Yunlong Chen 1,  Qian Du 1,  Chengbao Wang 1,  Pentao Liu 3,  Yiliang Miao 4,  Na Li 5,  Shiqiang Zhang 6,  Mingzhi Liao 7,  Jinlian Hua 8
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
  • 2 College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
  • 3 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Stem Cell and Regenerative Medicine Consortium, Pokfulam, Hong Kong.
  • 4 Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  • 5 College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: lina2017@nwafu.edu.cn.
  • 6 College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: shiqiangzhang@nwsuaf.edu.cn.
  • 7 College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: liaomz@nwsuaf.edu.cn.
  • 8 College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: jinlianhua@nwsuaf.edu.cn.
PMID: 38097188 DOI: 10.1016/j.jbc.2023.105556
Abstract

A renewable source of porcine macrophages derived from pluripotent stem cells (PSCs) would be a valuable alternative to primary porcine alveolar macrophages (PAMs) in the research of host-pathogen interaction mechanisms. We developed an efficient and rapid protocol, within 11 days, to derive macrophages from porcine PSCs (pPSCs). The pPSC-derived macrophages (pPSCdMs) exhibited molecular and functional characteristics of primary macrophages. The pPSCdMs showed macrophage-specific surface protein expression and macrophage-specific transcription factors, similar to PAMs. The pPSCdMs also exhibited the functional characteristics of macrophages, such as endocytosis, phagocytosis, PRRSV Infection and the response to lipopolysaccharide stimulation. Furthermore, we performed transcriptome Sequencing of the whole differentiation process to track the fate transitions of porcine PSCs involved in the signaling pathway. The activation of transforming growth factor beta (TGF-β) signaling was required for the formation of mesoderm and the inhibition of the TGF-β signaling pathway at the hematopoietic endothelium stage could enhance the fate transformation of hematopoiesis. In summary, we developed an efficient and rapid protocol to generate pPSCdMs that showed aspects of functional maturity comparable with PAMs. pPSCdMs could provide a broad prospect for the platforms of host-pathogen interaction mechanisms.

Keywords

TGF-β signaling pathway; hematopoiesis; macrophages; porcine pluripotent stem cells; rapid conversion.

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