Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Thành Chung Đặng; Yoko Ishii; Van De Nguyen; Seiji Yamamoto; Takeru Hamashima; Noriko Okuno; Quang Linh Nguyen; Yang Sang; Noriaki Ohkawa; Yoshito Saitoh; Mohammad Shehata; Nobuyuki Takakura; Toshihiko Fujimori; Kaoru Inokuchi; Hisashi Mori; Johanna Andrae; Christer Betsholtz; Masakiyo Sasahara

doi:10.1016/j.celrep.2019.03.084

Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Thành Chung Đặng, Yoko Ishii, Van De Nguyen, Seiji Yamamoto^*, Takeru Hamashima, Noriko Okuno, Quang Linh Nguyen, Yang Sang, Noriaki Ohkawa, Yoshito Saitoh, Mohammad Shehata, Nobuyuki Takakura, Toshihiko Fujimori, Kaoru Inokuchi, Hisashi Mori, Johanna Andrae, Christer Betsholtz, Masakiyo Sasahara

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin ⁺ immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

Original language	English
Pages (from-to)	1073-1089.e5
Journal	Cell Reports
Volume	27
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2019.03.084
State	Published - 2019/04/23

Keywords

PDGFRα
adult brain
differentiation
mesenchymal cell
oligodendrocyte progenitor cell
pericyte
regeneration

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2019.03.084

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Đặng, T. C., Ishii, Y., Nguyen, V. D., Yamamoto, S., Hamashima, T., Okuno, N., Nguyen, Q. L., Sang, Y., Ohkawa, N., Saitoh, Y., Shehata, M., Takakura, N., Fujimori, T., Inokuchi, K., Mori, H., Andrae, J., Betsholtz, C., & Sasahara, M. (2019). Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain. Cell Reports, 27(4), 1073-1089.e5. https://doi.org/10.1016/j.celrep.2019.03.084

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title = "Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain",

abstract = " Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin + immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.",

keywords = "PDGFRα, adult brain, differentiation, mesenchymal cell, oligodendrocyte progenitor cell, pericyte, regeneration",

author = "{\D}ặng, {Th{\`a}nh Chung} and Yoko Ishii and Nguyen, {Van De} and Seiji Yamamoto and Takeru Hamashima and Noriko Okuno and Nguyen, {Quang Linh} and Yang Sang and Noriaki Ohkawa and Yoshito Saitoh and Mohammad Shehata and Nobuyuki Takakura and Toshihiko Fujimori and Kaoru Inokuchi and Hisashi Mori and Johanna Andrae and Christer Betsholtz and Masakiyo Sasahara",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = apr,

day = "23",

doi = "10.1016/j.celrep.2019.03.084",

language = "英語",

volume = "27",

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Đặng, TC, Ishii, Y, Nguyen, VD, Yamamoto, S, Hamashima, T, Okuno, N, Nguyen, QL, Sang, Y, Ohkawa, N, Saitoh, Y, Shehata, M, Takakura, N, Fujimori, T, Inokuchi, K , Mori, H, Andrae, J, Betsholtz, C & Sasahara, M 2019, 'Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain', Cell Reports, vol. 27, no. 4, pp. 1073-1089.e5. https://doi.org/10.1016/j.celrep.2019.03.084

TY - JOUR

T1 - Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

AU - Đặng, Thành Chung

AU - Ishii, Yoko

AU - Nguyen, Van De

AU - Yamamoto, Seiji

AU - Hamashima, Takeru

AU - Okuno, Noriko

AU - Nguyen, Quang Linh

AU - Sang, Yang

AU - Ohkawa, Noriaki

AU - Saitoh, Yoshito

AU - Shehata, Mohammad

AU - Takakura, Nobuyuki

AU - Fujimori, Toshihiko

AU - Inokuchi, Kaoru

AU - Mori, Hisashi

AU - Andrae, Johanna

AU - Betsholtz, Christer

AU - Sasahara, Masakiyo

PY - 2019/4/23

Y1 - 2019/4/23

N2 - Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin + immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

AB - Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin + immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

KW - PDGFRα

KW - adult brain

KW - differentiation

KW - mesenchymal cell

KW - oligodendrocyte progenitor cell

KW - pericyte

KW - regeneration

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U2 - 10.1016/j.celrep.2019.03.084

DO - 10.1016/j.celrep.2019.03.084

M3 - 学術論文

C2 - 31018125

AN - SCOPUS:85064126661

SN - 2639-1856

VL - 27

SP - 1073-1089.e5

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Abstract

Keywords

ASJC Scopus subject areas

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