Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem/progenitor cell compartment
Guiying Shi
Xinyue Li
Keya Li
Yiying Huang
Xuepei Lei
Lin Bai
Chuan Qin
The Institute of Laboratory Animal Sciences,CAMS&PUMC,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,Beijing,P.R.China
摘要:Background : Hematopoietic stem cells (HSC) maintain the hematopoietic system ho-meostasis through self- renewal and multilineage differentiation potential. HSC are regulated by the microenvironment, cytokine signaling, and transcription factors. Recent results have shown that lipid pathways play a key role in the regulation of HSC quiescence, proliferation, and division. However, the mechanism by which lipid metabolism regulates HSC proliferation and differentiation remains to be clarified. Lipoprotein lipase (LPL) is an essential enzyme in the anabolism and catabolism of very low- density lipoprotein, chylomicrons, and triglyceride- rich lipoproteins. Methods : The percentage of hematopoietic stem/progenitor cells and immune cells were determined by fluorescence- activated cell sorting (FACS). The function and the mechanism of HSCs were analyzed by cell colony forming assay and qPCR analysis. The changes in LPL +/? HSC microenvironment were detected by transplantation as-says using red fluorescent protein (RFP) transgenic mice. Results : To explore the function of LPL in HSC regulation, heterozygous LPL- knockout mice (LPL +/? ) were established and analyzed by FACS. LPL +/? mice displayed de-creased hematopoietic stem/progenitor cell compartments. In vitro single- cell clono-genic assays and cell- cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57 KIP2 and p21 WAF1/CIP1 in LPL +/? mice was upregulated. Conclusions : LPL +/? mice exhibited HSC compartment impairment due to promotion of HSC proliferation, without any effects on the bone marrow (BM) microenvironment.
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论文发表日期:2021-12-25
在线出版日期:2025-08-15(本平台首次上网日期,不代表文献的发表时间)
页数:8( 418-425 )
英文信息展开
动物模型与实验医学(英文)

动物模型与实验医学(英文)

ISSN:2096-5451
年,卷(期):2021,4(4)
所属栏目:Original Articles