Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation

Hendrikse, Liam D.; Haldipur, Parthiv; Saulnier, Olivier; Millman, Jake; Sjoboen, Alexandria H.; Erickson, Anders W.; Ong, Winnie Peitee; Gordon, Victor; Coudière-Morrison, Ludivine; Mercier, Audrey; Shokouhian, Mohammad; Suárez, Raúl A.; Ly, Michelle; Borlase, Stephanie; Scott, David S.; Vladoiu, Maria C.; Farooq, Hamza; Sirbu, Olga; Nakashima, Takuma; Nambu, Shohei; Funakoshi, Yusuke; Bahcheli, Alec; Díaz-Mejía, J. Javier; Golser, Joseph; Bach, Kathleen; Phuong-Bao, Tram; Skowron, Patryk; Wang, Evan Y.; Kumar, Sachin; Balin, Polina; Visvanathan, Abhirami; Lee, John J.Y.; Ayoub, Ramy; Chen, Xin; Chen, Xiaodi; Mungall, Karen; Luu, Betty; Bérubé, Pierre R.; Wang, Yu C.; Pfister, Stefan M.; Kim, Seung-Ki; Delattre, Olivier; Bourdeaut, Franck; Doz, François; Masliah‐Planchon, Julien; Grajkowska, Wiesława; Loukides, James; Dirks, Peter B.; Fèvre‐Montange, Michelle; Jouvet, Anne; French, Pim J.; Kros, Johan M.; Zitterbart, Karel; Bailey, Swneke D.; Eberhart, Charles G.; Rao, Amulya A. Nageswara; Giannini, Caterina; Olson, James M.; Garami, Miklós; Hauser, Péter; Phillips, Joanna J.; Young, Stephanie; Torres, Carmen de; Mora, Jaume; Li, Kay K. W.; Ng, Ho‐Keung; Poon, Wai Sang; Pollack, Ian F.; López-Aguilar, Enrique; Gillespie, G. Yancey; Meter, Timothy E. Van; Shofuda, Tomoko; Vibhakar, Rajeev; Thompson, Reid C.; Cooper, Michael K.; Rubin, Joshua B.; Kumabe, Toshihiro; Jung, Shin; Lach, Bolesław; Iolascon, Achille; Ferrucci, Veronica; Antonellis, Pasqualino de; Zollo, Massimo; Cinalli, Giuseppe; Robinson, Shenandoah; Stearns, Duncan; Meir, Erwin G. Van; Porrati, Paola; Finocchiaro, Gaetano; Massimino, Maura; Carlotti, Carlos Gilberto; Faria, Cláudia; Roussel, Martine F.; Boop, Frederick A.; Chan, Jennifer A.; Aldinger, Kimberly A.; Razavi, F.; Silvestri, Evelina; McLendon, Roger E.; Thompson, Eric M.; Ansari, Marc; Garrè, Maria Luisa; Chico, F; Eguía, Pilar; Pérezpeña-Díazconti, Mario; Morrissy, A. Sorana; Cavalli, Florence M. G.; Wu, Xiaochong; Daniels, Craig; Rich, Jeremy; Jones, Steven J.M.; Moore, Richard A.; Marra, Marco A.; Huang, Xi; Reimand, Jüri; Sorensen, Poul H.; Wechsler‐Reya, Robert J.; Weiss, William A.; Pugh, Trevor J.; Garzia, Livia; Kleinman, Claudia L.; Stein, Lincoln; Jabado, Nada; Malkin, David; Ayrault, Olivier; Golden, Jeffrey A.; Ellison, David W.; Doble, Bradley W.; Ramaswamy, Vijay; Werbowetski-Ogilvie, Tamra E.; Suzuki, Hiromichi; Millen, Kathleen J.; Taylor, Michael D.

doi:10.1038/s41586-022-05578-0

Cited by 4 publications

(3 citation statements)

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“…We could speculate that OTX2 down-regulation may determine the activation of the pathways of cerebellar differentiation in MB cells. These data have great importance because the use of the combination of AA7.1, as specific targets of Prune-1, and SP-2577 molecules might also result at the interplay between Gr3 and Gr4 MB, with OTX-2 being an important component of Gr4 MB predisposition too [16].…”

Section: Discussionmentioning

confidence: 99%

“…In Gr3, we found that Prune-1 enhances the canonical TGF-β pathway followed by OTX2 and SNAIL up-regulation and PTEN down-regulation [15]. Furthermore, OTX2 maintains rhombic lip (RL) identity by inhibiting the CBFA complex until the cells exit the RL and differentiate [16]. The overexpression of OTX2 results in failed RL differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…The overexpression of OTX2 results in failed RL differentiation. The resulting ball of RL progenitor cells are retained with the RL in the nascent nodulus of the developing cerebellum, where ongoing mitotic activity eventually results in a mass lesion diagnosed as Gr3 or Gr4 MB [16]. Thus, OTX2 could be an important target for future therapies of MB.…”

Section: Introductionmentioning

confidence: 99%

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Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules

Bibbò,

Asadzadeh,

Boccia

et al. 2024

IJMS

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Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression. In this paper, we found that PRUNE-1 was transcriptionally regulated by lysine demethylase LSD1/KDM1A. This study aimed to investigate the therapeutic potential of inhibiting both PRUNE-1 and LSD1/KDM1A with the selective inhibitors AA7.1 and SP-2577, respectively. We found that the pharmacological inhibition had a substantial efficacy on targeting the metastatic axis driven by PRUNE-1 (PRUNE-1-OTX2-TGFβ-PTEN) in Gr3 MB. Using RNA seq transcriptomic feature data in Gr3 MB primary cells, we provide evidence that the combination of AA7.1 and SP-2577 positively affects neuronal commitment, confirmed by glial fibrillary acidic protein (GFAP)-positive differentiation and the inhibition of the cytotoxic components of the tumor microenvironment and the epithelial–mesenchymal transition (EMT) by the down-regulation of N-Cadherin protein expression. We also identified an impairing action on the mitochondrial metabolism and, consequently, oxidative phosphorylation, thus depriving tumors cells of an important source of energy. Furthermore, by overlapping the genomic mutational signatures through WES sequence analyses with RNA seq transcriptomic feature data, we propose in this paper that the combination of these two small molecules can be used in a second-line treatment in advanced therapeutics against Gr3 MB. Our study demonstrates that the usage of PRUNE-1 and LSD1/KDM1A inhibitors in combination represents a novel therapeutic approach for these highly aggressive metastatic MB tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules

Bibbò,

Asadzadeh,

Boccia

et al. 2024

IJMS

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Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development

Zhong,

Wang,

Huang

et al. 2023

Nat Commun

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Human cerebellar development is orchestrated by molecular regulatory networks to achieve cytoarchitecture and coordinate motor and cognitive functions. Here, we combined single-cell transcriptomics, spatial transcriptomics and single cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development. We revealed that combinations of transcription factors and cis-regulatory elements (CREs) play roles in governing progenitor differentiation and cell fate determination along trajectories in a hierarchical manner, providing a gene expression regulatory map of cell fate and spatial information for these cells. We also illustrated that granule cells located in different regions of the cerebellar cortex showed distinct molecular signatures regulated by different signals during development. Finally, we mapped single-nucleotide polymorphisms (SNPs) of disorders related to cerebellar dysfunction and discovered that several disorder-associated genes showed spatiotemporal and cell type-specific expression patterns only in humans, indicating the cellular basis and possible mechanisms of the pathogenesis of neuropsychiatric disorders.

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SARS-CoV-2 variant biology: immune escape, transmission and fitness

et al. 2023

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In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited a major step change in its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates of transmission relative to previous variants and were termed ‘variants of concern’ (VOCs). Designated Alpha, Beta, Gamma, Delta and Omicron, the VOCs emerged independently from one another, and in turn each rapidly became dominant, regionally or globally, outcompeting previous variants. The success of each VOC relative to the previously dominant variant was enabled by altered intrinsic functional properties of the virus and, to various degrees, changes to virus antigenicity conferring the ability to evade a primed immune response. The increased virus fitness associated with VOCs is the result of a complex interplay of virus biology in the context of changing human immunity due to both vaccination and prior infection. In this Review, we summarize the literature on the relative transmissibility and antigenicity of SARS-CoV-2 variants, the role of mutations at the furin spike cleavage site and of non-spike proteins, the potential importance of recombination to virus success, and SARS-CoV-2 evolution in the context of T cells, innate immunity and population immunity. SARS-CoV-2 shows a complicated relationship among virus antigenicity, transmission and virulence, which has unpredictable implications for the future trajectory and disease burden of COVID-19.

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Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation

Cited by 4 publications

References 0 publications

Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules

Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules

Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development

SARS-CoV-2 variant biology: immune escape, transmission and fitness

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