Lipopolysaccharide induces aging phenotype of hematopoietic stem cells in bone marrow and spleen of young mice
10.3969/j.issn.1000-4718.2024.01.005
- VernacularTitle:脂多糖诱导年轻小鼠骨髓及脾脏造血干细胞衰老表型的作用研究
- Author:
Ke BAI
1
;
Mi ZOU
;
Qiang ZHAN
;
Yingxin HUANG
;
Zhenyu JU
;
Zhiyang CHEN
Author Information
1. 暨南大学教育部再生医学重点实验室,衰老与再生医学研究院,生命科学技术学院,广东 广州 510632
- Keywords:
inflammation;
hematopoietic stem cells;
aging;
extramedullary hematopoiesis;
myeloid differen-tiation
- From:
Chinese Journal of Pathophysiology
2024;40(1):38-46
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.
