Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem/progenitor cell compartment

Abstract

Abstract Background Hematopoietic stem cells (HSC) maintain the hematopoietic system homeostasis 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 assays 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 decreased hematopoietic stem/progenitor cell compartments. In vitro single‐cell clonogenic assays and cell‐cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57KIP2 and p21WAF1/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.

Keywords

• cell cycle
• HSCs
• LPL