TY - JOUR
T1 - GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma
AU - Natsumeda, Manabu
AU - Miyahara, Hiroaki
AU - Yoshimura, Junichi
AU - Nakata, Satoshi
AU - Nozawa, Takanori
AU - Ito, Junko
AU - Kanemaru, Yu
AU - Watanabe, Jun
AU - Tsukamoto, Yoshihiro
AU - Okada, Masayasu
AU - Oishi, Makoto
AU - Hirato, Junko
AU - Wataya, Takafumi
AU - Ahsan, Sama
AU - Tateishi, Kensuke
AU - Yamamoto, Tetsuya
AU - Rodriguez, Fausto J.
AU - Takahashi, Hitoshi
AU - Hovestadt, Volker
AU - Suva, Mario L.
AU - Taylor, Michael D.
AU - Eberhart, Charles G.
AU - Fujii, Yukihiko
AU - Kakita, Akiyoshi
N1 - Funding Information:
M.N. (17K16632, 19K09476), M.O.k. (17K17739, 20K17955), J.W. (19K18418), and Y.T. (17K17735) have received funding from Japan Society for Promotion of Science (JSPS). M.N. has received funding for a Gli3 animal model project by AdAMS (16H06276). C.G.E. has received funding from JSPS Invitational Fellowship Programs for Overseas Research in Japan and Niigata University Brain Research Institute Global Collaborative Project 2018 and Y.F. has received funding from Japan-US Brain Research Cooperation Program for this project. The authors would like to acknowledge C. Tanda, J. Takasaki, and S. Nigorikawa for their technical assistance.
Publisher Copyright:
© 2020 American Association of Neuropathologists, Inc. All rights reserved.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.
AB - Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.
KW - GLI3
KW - Medulloblastoma
KW - Nanostring analysis
KW - Neuronal differentiation
KW - Single cell RNA sequencing
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U2 - 10.1093/jnen/nlaa141
DO - 10.1093/jnen/nlaa141
M3 - Article
C2 - 33249504
AN - SCOPUS:85100280842
SN - 0022-3069
VL - 80
SP - 129
EP - 136
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 2
ER -