Dataset Information

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.

ABSTRACT: 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.

SUBMITTER: Rivera-Torruco G

PROVIDER: S-EPMC8993550 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Rivera-Torruco Guadalupe G Martínez-Mendiola Carolina A CA Angeles-Floriano Tania T Jaimes-Ortega Gustavo Alberto GA Maravillas-Montero José Luis JL García-Contreras Rodolfo R González Yolanda Y Juárez Esmeralda E Nava Porfirio P Ortiz-Navarrete Vianney V Medina-Contreras Oscar O Licona-Limón Paula P Valle-Rios Ricardo R

Journal of immunology research 20220401

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 hematopoie ...[more]

PMID: 35402623

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Project description:Background: Sepsis is life-threatening organ dysfunction associated with high risk of death. The immune response of sepsis is complex and varies over time. The immune cells are derived from hematopoietic stem and progenitor cells (HSPCs) which can respond to many infections. Our previous study found that sepsis causes HSPC dysregulation in mouse. But few studies have previously investigated the kinetics of HSPC and its contribution to immune system in sepsis patients. Purpose: We aimed to identify the kinetics of HSPCs and their contribution to immune system in sepsis patients. Methods: We enrolled eight sepsis patients and five healthy control subjects. Peripheral blood (PB) samples from each patient were collected three times: on the first, fourth, and seventh days, once from each healthy control subject. Peripheral blood mononuclear cells (PBMCs) were isolated by density centrifugation and stained with cocktails of antibodies. Populations of HSPCs and their subpopulation were analyzed by flow cytometry. Immune cells were characterized by flow cytometry and blood cell analysis. Correlations between HSPCs and immune cells were analyzed using the Pearson correlation test. Results: We found that the frequency of HSPCs (CD34+ cells and CD34+CD38+ cells) in sepsis patients on day 4 was significantly higher than that in the healthy controls. The most pronounced change in subpopulation analysis is the frequency of common myeloid progenitors (CMPs; CD34+CD38+CD135+CD45RA-). But no difference in the immunophenotypically defined hematopoietic stem cells (HSCs; CD34+CD38-CD90+CD45RA-) in sepsis patients was observed due to rare HSC numbers in PB. The number of PBMCs and lymphocytes are decreased, whereas the white blood cell (WBC) and neutrophil counts were increased in sepsis patients. Importantly, we found a negative correlation between CD34+ on day 1 and WBC and lymphocytes on day 4 from correlation analysis in sepsis patients. Conclusion: The present study demonstrated that the HSPC and its subpopulation in sepsis patients expanded. Importantly, the changes in HSPCs at early time points in sepsis patients have negative correlations with later immune cells. Our results may provide a novel diagnostic indicator and a new therapeutic approach.

Dataset Information

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.

Publications

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

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Dataset Information

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.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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.