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A2B5+/GFAP+ Cells of Rat Spinal Cord Share a Similar Lipid Profile with Progenitor Cells: A Comparative Lipidomic Study

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Abstract

The central nervous system (CNS) harbors multiple glial fibrillary acidic protein (GFAP) expressing cell types. In addition to the most abundant cell type of the CNS, the astrocytes, various stem cells and progenitor cells also contain GFAP+ populations. Here, in order to distinguish between two types of GFAP expressing cells with or without the expression of the A2B5 antigens, we performed lipidomic analyses on A2B5+/GFAP+ and A2B5−/GFAP+ cells from rat spinal cord. First, A2B5+/GFAP− progenitors were exposed to the leukemia inhibitory factor (LIF) or bone morphogenetic protein (BMP) to induce their differentiation to A2B5+/GFAP+ cells or A2B5−/GFAP+ astrocytes, respectively. The cells were then analyzed for changes in their phospholipid, sphingolipid or acyl chain profiles by mass spectrometry and gas chromatography. Compared to A2B5+/GFAP− progenitors, A2B5−/GFAP+ astrocytes contained higher amounts of ether phospholipids (especially the species containing arachidonic acid) and sphingomyelin, which may indicate characteristics of cellular differentiation and inability for multipotency. In comparison, principal component analyses revealed that the lipid composition of A2B5+/GFAP+ cells retained many of the characteristics of A2B5+/GFAP− progenitors, but their lipid profile was different from that of A2B5−/GFAP+ astrocytes. Thus, our study demonstrated that two GFAP+ cell populations have distinct lipid profiles with the A2B5+/GFAP+ cells sharing a phospholipid profile with progenitors rather than astrocytes. The progenitor cells may require regulated low levels of lipids known to mediate signaling functions in differentiated cells, and the precursor lipid profiles may serve as one measure of the differentiation capacity of a cell population.

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Abbreviations

BMP:

Bone morphogenetic protein

CERS2:

Ceramide synthase 2

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

FA:

Fatty acid

gp130:

Membrane glycoprotein 130

GFAP:

Glial fibrillary acidic protein

GlcCer:

Glucosylceramide

GRP:

Glial restricted precursor

GRP-LIF:

GRP and LIF-stimulated A2B5+/GFAP+ cell

IL-6:

Interleukin 6

JAK:

Janus kinase

LIF:

Leukemia inhibitory factor

MUFA:

Monounsaturated fatty acid

PC:

Phosphatidylcholine

PCA:

Principal component analysis

PE:

Phosphatidylethanolamine

PGE2:

Prostaglandin E2

PI:

Phosphatidylinositol

PL:

Phospholipid

PS:

Phosphatidylserine

PUFA:

Polyunsaturated fatty acid

SFA:

Saturated fatty acid

SIMCA:

Soft independent modeling of class analogy

SL:

Sphingolipid

SM:

Sphingomyelin

STAT:

Signal transducer and activator of transcription

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Acknowledgments

We thank Agnès Viherä, Lea Armassalo, Tarja Grundström, Eliisa Kekäläinen, Aaro Miettinen, and Johanna Mäkelä for excellent technical assistance, the Molecular Imaging Unit of Biomedicum Helsinki for the use of their instrument and for assistance, and Dr. Masaaki Kitada for helpful comments on this research. This work was supported in part by a fellowship funding from Academy of Finland (No. 111261 to RK), grants from Japan Brain Foundation (YI), the Nakayama Foundation of Human Science (YI), and the Mizutani Foundation for Glycoscieince (150026 to YI).

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Itokazu, Y., Tajima, N., Kerosuo, L. et al. A2B5+/GFAP+ Cells of Rat Spinal Cord Share a Similar Lipid Profile with Progenitor Cells: A Comparative Lipidomic Study. Neurochem Res 41, 1527–1544 (2016). https://doi.org/10.1007/s11064-016-1867-3

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