Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Chung, Dang Thanh; Ikoma, Yoko; Nguyen, Van De; Yamamoto, Seiji; Hamashima, Takeru; Okuno, Noriko; Nguyen, Quang Linh; Yang, Shi Yu; Ohkawa, Noriaki; Saitoh, Yoshito; Shehata, Mohammad; Takakura, Nobuyuki; Fujimori, Toshihiko; Inokuchi, Kaoru; Mori, Hisashi; Andræ, Johanna; Betsholtz, Christer; Sasahara, Masakiyo

doi:10.1016/j.celrep.2019.03.084

Cited by 55 publications

(28 citation statements)

References 71 publications

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“…Here, we report the widespread distribution pattern of the C9C5 immunoreactivity in the adult mouse brain and show that C9C5 antibody marks a subset of CC1 + (11-12%), Olig2 + and Sox10 + (3-6%), CAIImature oligodendrocytes as quantified in the cerebral cortex and in the hypothalamus. These cells do not express the PDGFRα signal implicated in OPCs proliferation and in the inhibition of the expression of oligodendroglial maturation markers such as CC1 [18,20]. Thus, these mature oligodendroglial cells constitute a source for delivering Shh to brain cells.…”

Section: Discussionmentioning

confidence: 99%

C9C5 positive mature oligodendrocytes are a source of Sonic Hedgehog in the mouse brain

et al. 2020

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In the mature rodent brain, Sonic Hedgehog (Shh) signaling regulates stem and progenitor cell maintenance, neuronal and glial circuitry and brain repair. However, the sources and distribution of Shh mediating these effects are still poorly characterized. Here, we report in the adult mouse brain, a broad expression pattern of Shh recognized by the specific monoclonal C9C5 antibody in a subset (11-12%) of CC1 + mature oligodendrocytes that do not express carbonic anhydrase II. These cells express also Olig2 and Sox10, two oligodendrocyte lineage-specific markers, but not PDGFRα, a marker of oligodendrocyte progenitors. In agreement with oligodendroglial cells being a source of Shh in the adult mouse brain, we identify Shh transcripts by single molecule fluorescent in situ hybridization in a subset of cells expressing Olig2 and Sox10 mRNAs. These findings also reveal that Shh expression is more extensive than originally reported. The Shh-C9C5-associated signal labels the oligodendroglial cell body and decorates by intense puncta the processes. C9C5 + cells are distributed in a grid-like manner. They constitute small units that could deliver locally Shh to its receptor Patched expressed in GFAP + and S100β + astrocytes, and in HuC/D + neurons as shown in Ptc LacZ/+ reporter mice. Postnatally, C9C5 immunoreactivity overlaps the myelination peak that occurs between P10 and P20 and is down regulated during ageing. Thus, our data suggest that C9C5 + CC1 + oligodendroglial cells are a source of Shh in the mouse postnatal brain.

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Section: Discussionmentioning

confidence: 99%

C9C5 positive mature oligodendrocytes are a source of Sonic Hedgehog in the mouse brain

et al. 2020

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“…Interestingly, an unbiased analysis of the top 25 differentially expressed genes revealed that SOX10 and PDGFRA are strongly downregulated after cilium induction. Studies have demonstrated that PDGFRA is rapidly downregulated together with oligodendrocyte progenitor (OPC) lineage markers of SOX10 and OLIG2 when OPC differentiate into oligodendrocytes (äặng et al, 2019;Rivers et al, 2008). Notably, downregulation of stemness maintenance and cell cycle regulators implicate cilium induction switches GSCs from self-renewal to differentiation state (Figures S7E and S7F).…”

Section: Cilium Induction Resets the Aberrant Pdgfr-a Signaling In Opc-like Gscsmentioning

confidence: 99%

Cilium induction triggers differentiation of glioma stem cells

Goranci-Buzhala¹,

Mariappan²,

Ricci–Vitiani³

et al. 2021

Cell Reports

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“…Platelet-derived growth factors (PDGFs) and their cognate receptors compose a signaling network that consists of five ligand-dimers (PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, PDGF-DD) and three receptors (PDGFR-αα, PDGFR-ββ, PDGFR-αβ) ( 175 ). While PDGFs have originally been identified as growth factor for smooth muscle cells ( 176 ), they are nowadays viewed as potent inducer of oligodendrocyte proliferation and differentiation ( 177 , 178 ). Interestingly, the PDGF family of cysteine-knot growth factors also includes members of the VEGF subfamily, of which VEGF-B has been shown to induce pro-inflammatory gene expression in astrocytes ( 48 ).…”

Section: Protective Effects Of Reactive Astrocytes Following Cns Insumentioning

confidence: 99%

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

2020

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Astrocytes play important roles in numerous central nervous system disorders including autoimmune inflammatory, hypoxic, and degenerative diseases such as Multiple Sclerosis, ischemic stroke, and Alzheimer's disease. Depending on the spatial and temporal context, activated astrocytes may contribute to the pathogenesis, progression, and recovery of disease. Recent progress in the dissection of transcriptional responses to varying forms of central nervous system insult has shed light on the mechanisms that govern the complexity of reactive astrocyte functions. While a large body of research focuses on the pathogenic effects of reactive astrocytes, little is known about how they limit inflammation and contribute to tissue regeneration. However, these protective astrocyte pathways might be of relevance for the understanding of the underlying pathology in disease and may lead to novel targeted approaches to treat autoimmune inflammatory and degenerative disorders of the central nervous system. In this review article, we have revisited the emerging concept of protective astrocyte functions and discuss their role in the recovery from inflammatory and ischemic disease as well as their role in degenerative disorders. Focusing on soluble astrocyte derived mediators, we aggregate the existing knowledge on astrocyte functions in the maintenance of homeostasis as well as their reparative and tissue-protective function after acute lesions and in neurodegenerative disorders. Finally, we give an outlook of how these mediators may guide future therapeutic strategies to tackle yet untreatable disorders of the central nervous system.

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Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Abstract: Highlights d Oligodendrocyte progenitor cells (OPCs) disappeared and then repopulated in CAGG-iKO mice d Repopulated OPCs are partly derived from pericyte and/or mesenchymal cell population (PC/MC) d PC/MC-derived OPCs differentiate into MBP-expressing mature oligodendrocytes

Cited by 55 publications

References 71 publications

C9C5 positive mature oligodendrocytes are a source of Sonic Hedgehog in the mouse brain

C9C5 positive mature oligodendrocytes are a source of Sonic Hedgehog in the mouse brain

Cilium induction triggers differentiation of glioma stem cells

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult

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