Isthmin 1 is Expressed by Progenitor-Like Cells in the Lung: Phenotypical Analysis of Isthmin 1+ Hematopoietic Stem-Like Cells in Homeostasis and during Infection

• Published in: Journal of immunology research Vol. 2022; pp. 2909487 - 13
• Main Authors: Rivera-Torruco, Guadalupe, Martínez-Mendiola, Carolina A., Angeles-Floriano, Tania, Jaimes-Ortega, Gustavo Alberto, Maravillas-Montero, José Luis, García-Contreras, Rodolfo, González, Yolanda, Juárez, Esmeralda, Nava, Porfirio, Ortiz-Navarrete, Vianney, Medina-Contreras, Oscar, Licona-Limón, Paula, Valle-Rios, Ricardo
• Format: Journal Article
• Language: English
• Published: Egypt Hindawi 01-04-2022; Hindawi Limited
• Subjects: Animals; Blood cells; Bone marrow; c-Kit protein; Ethics; Flow cytometry; Hematopoiesis; Hematopoietic Stem Cells; Homeostasis; Immunology; Infections; Inflammation; Intercellular Signaling Peptides and Proteins - metabolism; Laboratory animals; Localization; Lung - metabolism; Lungs; Mesenchyme; Mice; Mice, Inbred C57BL; Progenitor cells; Proteins; Sepsis; Sepsis - metabolism; Small intestine; Software; Stem cell transplantation; TLR4 protein; TLR5 protein; TLR9 protein; Toll-like receptors
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2022/2909487

The process by which blood cells are generated has been widely studied in homeostasis and during pathogen-triggered inflammatory response. Recently, murine lungs have been shown to be a significant source of hematopoietic progenitors in a process known as extramedullary hematopoiesis. Using multiparametric flow cytometry, we have identified mesenchymal, endothelial, and hematopoietic progenitor cells that express the secreted small protein Isthmin 1 (ISM1). Further characterization of hematopoietic progenitor cells indicated that ISM1+ Lineage- Sca-1+ c-kit+ (ISM1+ LSK) cells are enriched in short-term hematopoietic stem cells (ST-HSCs). Moreover, most Sca-1+ ISM1+ cells express the residence marker CD49a, and this correlated with their localization in the extravascular region of the lung, indicating that ISM1+ cells are lung-resident cells. We also observed that ISM1+ cells express TLR4, TLR5, and TLR9, and, in a mouse model of sepsis induced by P. aeruginosa, we observed that all the LSK and ISM1+LSK cells were affected. We conclude that ISM1 is a novel biomarker associated with progenitor-like cells. ISM1+ cells are involved in the response to a bacterial challenge, suggesting an association between ISM1-producing cells and dangerous inflammatory responses like sepsis.