Integrated Lipidomics and Transcriptomics Characterization upon Aging-Related Changes of Lipid Species and Pathways in Human Bone Marrow Mesenchymal Stem Cells

Aberrant differentiations of bone
mesenchymal stem cells (BMSCs)
have proved to be associated with the occurrence of senile osteoporosis.
However, mechanisms of this phenomenon relative to abnormal lipid
metabolism remain unclear. This study was conducted to characterize
the lipidomics alterations during BMSC passaging, aiming at uncovering
the aging-related lipid metabolism that may play an important role
in aberrant differentiations of BMSCs. Principal component analysis
presented the sequential lipidomics alterations during BMSC passaging.
The majority of glycerophospholipids, including phosphatidylcholines,
phosphatidylethanolamines, phosphatidylglycerols, as well as sphingolipids,
revealed significant elevations, whereas the others, including phosphatidic
acids, phosphatidylinositols, and phosphatidylserines, presented decreases
in aged cells. Double-bond equivalent versus carbon number plots demonstrated
that the changing trends and significances of lipids during passaging
were associated with the chain length and the degree of unsaturation.
In the correlation networks, the scattering patterns of lipid categories
suggested the category-related metabolic independence and potential
conversion among phosphatidic acids, phosphatidylinositols, and phosphatidylserines.
The lipid–enzyme integrated pathway analysis indicated the
activated metabolic conversion from phosphatidic acids to CDP-diacylglycerol
to phosphatidylinositols and from sphingosine to ceramides to sphingomyelins
with BMSC passaging. The conversions among lipid species described
the lipidomics responses that potentially induced the aberrant differentiations
during BMSC aging.

骨髓间充质干细胞（bone mesenchymal stem cells, BMSCs）的异常分化已被证实与老年性骨质疏松的发生密切相关。然而，该现象与脂质代谢异常之间的具体调控机制仍未明确。本研究旨在刻画骨髓间充质干细胞传代过程中的脂质组学（lipidomics）变化，以期揭示可能在骨髓间充质干细胞异常分化中发挥关键作用的衰老相关脂质代谢机制。主成分分析（Principal component analysis）结果显示，骨髓间充质干细胞传代过程中存在渐进式的脂质组学改变。绝大多数甘油磷脂（glycerophospholipids），包括磷脂酰胆碱（phosphatidylcholines）、磷脂酰乙醇胺（phosphatidylethanolamines）、磷脂酰甘油（phosphatidylglycerols）以及鞘脂（sphingolipids），在衰老细胞中均呈现显著上调；而其余脂质类别，如磷脂酸（phosphatidic acids）、磷脂酰肌醇（phosphatidylinositols）与磷脂酰丝氨酸（phosphatidylserines）则表达下调。双键当量-碳数绘图结果表明，传代过程中脂质的变化趋势与显著性水平与其碳链长度及不饱和程度密切相关。在相关网络中，脂质类别的分布模式提示，磷脂酸、磷脂酰肌醇与磷脂酰丝氨酸之间存在类别相关的代谢独立性及潜在的代谢转化关系。脂质-酶整合通路分析结果显示，随着骨髓间充质干细胞传代，两条代谢转化通路被激活：一是从磷脂酸经CDP-二酰甘油（CDP-diacylglycerol）转化为磷脂酰肌醇，二是从鞘氨醇（sphingosine）经神经酰胺（ceramides）转化为鞘磷脂（sphingomyelins）。各类脂质之间的转化模式，揭示了可能在骨髓间充质干细胞衰老过程中诱导其异常分化的脂质组学应答机制。