Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells

Sharifi, Kazem; Ebrahimi, Majid; Kagawa, Yoshiteru; Islam, Ariful; Tuerhong, Tuerxun; Yasumoto, Yuki; Hara, Tomonori; Yamamoto, Yoshiyuki; Miyazaki, Hirofumi; Tokuda, Nobuko; Yoshikawa, Takeo; Owada, Yuji

doi:10.1007/s00441-013-1730-7

Cited by 41 publications

(27 citation statements)

References 51 publications

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“…We first examined localization of FABP7 in the mouse mPFC. Consistent with our former findings (Owada et al, ; Sharifi et al, ), FABP7 was localized in GFAP + astrocytes (Supp. Info.…”

Section: Resultssupporting

confidence: 93%

Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons

Ebrahimi

Yamamoto

Sharifi

et al. 2015

Glia

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Fatty acid binding protein 7 (FABP7) expressed by astrocytes in developing and mature brains is involved in uptake and transportation of fatty acids, signal transduction, and gene transcription. Fabp7 knockout (Fabp7 KO) mice show behavioral phenotypes reminiscent of human neuropsychiatric disorders such as schizophrenia. However, direct evidence showing how FABP7 deficiency in astrocytes leads to altered brain function is lacking. Here, we examined neuronal dendritic morphology and synaptic plasticity in medial prefrontal cortex (mPFC) of Fabp7 KO mice and in primary cortical neuronal cultures. Golgi staining of cortical pyramidal neurons in Fabp7 KO mice revealed aberrant dendritic morphology and decreased spine density compared with those in wild-type (WT) mice. Aberrant dendritic morphology was also observed in primary cortical neurons co-cultured with FABP7-deficient astrocytes and neurons cultured in Fabp7 KO astrocyte-conditioned medium. Excitatory synapse number was decreased in mPFC of Fabp7 KO mice and in neurons co-cultured with Fabp7 KO astrocytes. Accordingly, whole-cell voltage-clamp recording in brain slices from pyramidal cells in the mPFC showed that both amplitude and frequency of action potential-independent miniature excitatory postsynaptic currents (mEPSCs) were decreased in Fabp7 KO mice. Moreover, transplantation of WT astrocytes into the mPFC of Fabp7 KO mice partially attenuated behavioral impairments. Collectively, these results suggest that astrocytic FABP7 is important for dendritic arbor growth, neuronal excitatory synapse formation, and synaptic transmission, and provide new insights linking FABP7, lipid homeostasis, and neuropsychiatric disorders, leading to novel therapeutic interventions.

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“…We first examined localization of FABP7 in the mouse mPFC. Consistent with our former findings (Owada et al, ; Sharifi et al, ), FABP7 was localized in GFAP + astrocytes (Supp. Info.…”

Section: Resultssupporting

confidence: 93%

Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons

Ebrahimi

Yamamoto

Sharifi

et al. 2015

Glia

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“…Similarly, the proportion of OPCs differentiating into MBP + /OLIG2 + myelin‐sheath forming oligodendrocytes is also significantly reduced (WT: 27% MBP + /OLIG2 + cells, Fabp7 KD: 5% MBP + /OLIG2 + cells, p = .03, unpaired Student's t ‐test) (Figure d,g). These findings concur with a study by Sharifi and colleagues, whose data was also consistent with a role for FABP7 in OPC differentiation (Sharifi et al, ). In the same publication it was also shown that the knockout of Fabp7 ( Fabp7 KO) affected the OPC proliferation capacity in vitro (Sharifi et al, ).…”

Section: Resultssupporting

confidence: 93%

“…There are ten FA binding proteins (FABPs), of which FABP3, FABP5, and FABP7 are expressed in the CNS (Owada, Yoshimoto, & Kondo, ). FABP7 is mainly expressed in astrocytes (Owada et al, ) and oligodendrocyte progenitor cells (OPCs; Sharifi et al, ), a progenitor cell giving rise to mature oligodendrocytes (OLs) in development and in response to injury (Franklin & ffrench‐Constant, ). OPCs isolated from Fabp7 knockout ( Fabp7 KO) mice have impaired differentiation in vitro (Sharifi et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…FABP7 is mainly expressed in astrocytes (Owada et al, ) and oligodendrocyte progenitor cells (OPCs; Sharifi et al, ), a progenitor cell giving rise to mature oligodendrocytes (OLs) in development and in response to injury (Franklin & ffrench‐Constant, ). OPCs isolated from Fabp7 knockout ( Fabp7 KO) mice have impaired differentiation in vitro (Sharifi et al, ). In animal models of primary demyelination, Fabp7 expression is increased in CNS resident cells (Bannerman, Hahn, Soulika, Gallo, & Pleasure, ; Huang et al, ; Kipp et al, ).…”

Section: Introductionmentioning

confidence: 99%

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The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination

Foerster

Fuente

Kagawa

et al. 2020

Glia

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The major constituents of the myelin sheath are lipids, which are made up of fatty acids (FAs). The hydrophilic environment inside the cells requires FAs to be bound to proteins, preventing their aggregation. Fatty acid binding proteins (FABPs) are one class of proteins known to bind FAs in a cell. Given the crucial role of FAs for myelin sheath formation we investigated the role of FABP7, the major isoform expressed in oligodendrocyte progenitor cells (OPCs), in developmental myelination and remyelination. Here, we show that the knockdown of Fabp7 resulted in a reduction of OPC differentiation in vitro. Consistent with this result, a delay in developmental myelination was observed in Fabp7 knockout animals. This delay was transient with full myelination being established before adulthood. FABP7 was dispensable for remyelination, as the knockout of Fapb7 did not alter remyelination efficiency in a focal demyelination model. In summary, while FABP7 is important in OPC differentiation in vitro, its function is not crucial for myelination and remyelination in vivo. K E Y W O R D Sfatty acid binding protein, myelination, remyelination, OPC

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“…Instead, a seperate factor active at the right-hand site of the astrocyte cluster (figure 2C) suggests that there exists an intermediate checkpoint between the astrocytes and OPCs. This factor is characterized by the highly variable Fabp7 , a regulator of both astrocytes as well as OPCs (14, 15). Further effect of the cell cycle can be observed in the small set of protruding cells in the OPC 2 cluster as it is no longer present in the last embedding.…”

Section: Resultsmentioning

confidence: 99%

Untangling biological factors influencing trajectory inference from single cell data

Charrout

Reinders

Mahfouz

2020

Preprint

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Advances in single-cell RNA sequencing over the past decade has shifted the discussion of cell identity towards the transcriptional state of the cell. While the incredible resolution provided by singlecell RNA sequencing has led to great advances in unravelling tissue heterogeneity and inferring cell differentiation dynamics, it raises the question of which sources of variation are important for determining cellular identity. Here we show that confounding biological sources of variation, most notably the cell cycle, can distort the inference of differentiation trajectories. We show that by factorizing single cell data into distinct sources of variation, we can select a relevant set of factors that constitute the core regulators for trajetory inference, while filtering out confounding sources of variation (e.g. cell cycle) which can perturb the inferred trajectory. Script are available publicly on https://github.com/mochar/cell_variation. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 single cell | pseudotime | factor analysis | trajectory inference S ingle cell RNA-sequencing enables quantitative gene ex-1 pression profiling of individual cells. From an RNA view-2 point, these cells live in a high-dimensional space defined by the 3 expression of their genes. A critical step when analyzing such 4data is the identification of cells in order to find and label the 5 cell types present in the data. This is often achieved by group-6 ing together cells with similar expression profiles by applying 7 a clustering method. The resulting cell clusters are thus sepa-8 rated from one another by a set of genes uniquely expressed or 9 silenced in a subset of clusters. These so-called marker genes 10 can then be used for identification by cross-referencing with 11 known marker genes or marker genes found in other studies. 12This clustering-based approach for cell identification relies on 13 the general presumption that the measured expression lev-14 els are reflective of the cell's identity, which may be violated 15 due to shared transcriptional programs between two or more 16 types. Large variations within cell type clusters due to many 17 exclusive programs may also pose a problem as it can become 18 hard to discern between cell types and cell states (1). More 19 generally, sources of variation that contribute significantly to 20 the cell-cell distances in gene space, yet do not reflect the cell 21 type, can be detrimental to the identification task. These can 22 vary from small transient changes e.g. cell communication, 23 up to complex shifts in the cell's regulatory state such as the 24 cell cycle, which has been reported to contribute a substantial 25 portion of the gene expression variance (2). Moreover, cell 26 identification is often preceded by a gene filtering step whereby 27 genes with low variance (and therefore little information) are 28 discarded to ease the computational burden in downstream 29 analysis. Depending on the normalization and filtering criteria 30 used, gene filtering can lead to a lower dimensional space that 31 f...

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Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells

Cited by 41 publications

References 51 publications

Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons

Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons

The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination

Untangling biological factors influencing trajectory inference from single cell data

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