New Results
Single-cell transcriptomic profile reveals macrophage heterogeneity in medulloblastoma and their treatment-dependent recruitment
Mai T. Dang, Michael Gonzalez, Krutika S. Gaonkar, Komal S. Rathi, Patricia Young, Sherjeel Arif, Li Zhai, Md Zahidul Alam, Samir Devalaraja, Tsun Ki To, Ian W. Folkert, Pichai Ramen, Jo Lynne Rokita, Daniel Martinez, Jaclyn N. Taroni, Joshua Shapiro, View ORCID ProfileCasey S. Greene, Candace Savonen, View ORCID ProfileHakon Hakonarson, Tom Curran, Malay Haldar
doi: https://doi.org/10.1101/2020.02.12.945642
Mai T. Dang
1Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
2Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Michael Gonzalez
3Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Krutika S. Gaonkar
4Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
5Department of Bioinformatics and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
6Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Komal S. Rathi
4Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
5Department of Bioinformatics and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
6Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Patricia Young
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Sherjeel Arif
4Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
5Department of Bioinformatics and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
6Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Li Zhai
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Md Zahidul Alam
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Samir Devalaraja
2Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
9Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Tsun Ki To
2Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Ian W. Folkert
2Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
10Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Pichai Ramen
4Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
5Department of Bioinformatics and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
6Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jo Lynne Rokita
4Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
5Department of Bioinformatics and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
6Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Daniel Martinez
11Pathology Core, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jaclyn N. Taroni
7Alex’s Lemonade Stand Foundation for Childhood Cancer, Bala Cynwyd, PA, USA
Joshua Shapiro
7Alex’s Lemonade Stand Foundation for Childhood Cancer, Bala Cynwyd, PA, USA
Casey S. Greene
7Alex’s Lemonade Stand Foundation for Childhood Cancer, Bala Cynwyd, PA, USA
12Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA
Candace Savonen
7Alex’s Lemonade Stand Foundation for Childhood Cancer, Bala Cynwyd, PA, USA
Hakon Hakonarson
3Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
13Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Tom Curran
14Children’s Research Institute at Mercy Children’s Hospital, Kansas City, KA, USA
Malay Haldar
2Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
8Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
9Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Abstract
The role of macrophages in medulloblastoma, the most common malignant pediatric brain tumor, is unclear. Using single-cell RNA sequencing in a mouse model of sonic hedgehog medulloblastoma and analysis of bulk RNA sequencing of human medulloblastoma, we investigated macrophage heterogeneity. Our findings reveal differential recruitment of macrophages with molecular-targeted versus radiation therapy and identify an immunosuppressive monocyte-derived macrophages following radiation treatment of mouse medulloblastoma, uncovering potential strategies for immunomodulation as adjunctive therapy.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted February 13, 2020.
Single-cell transcriptomic profile reveals macrophage heterogeneity in medulloblastoma and their treatment-dependent recruitment
Mai T. Dang, Michael Gonzalez, Krutika S. Gaonkar, Komal S. Rathi, Patricia Young, Sherjeel Arif, Li Zhai, Md Zahidul Alam, Samir Devalaraja, Tsun Ki To, Ian W. Folkert, Pichai Ramen, Jo Lynne Rokita, Daniel Martinez, Jaclyn N. Taroni, Joshua Shapiro, Casey S. Greene, Candace Savonen, Hakon Hakonarson, Tom Curran, Malay Haldar
bioRxiv 2020.02.12.945642; doi: https://doi.org/10.1101/2020.02.12.945642
Single-cell transcriptomic profile reveals macrophage heterogeneity in medulloblastoma and their treatment-dependent recruitment
Mai T. Dang, Michael Gonzalez, Krutika S. Gaonkar, Komal S. Rathi, Patricia Young, Sherjeel Arif, Li Zhai, Md Zahidul Alam, Samir Devalaraja, Tsun Ki To, Ian W. Folkert, Pichai Ramen, Jo Lynne Rokita, Daniel Martinez, Jaclyn N. Taroni, Joshua Shapiro, Casey S. Greene, Candace Savonen, Hakon Hakonarson, Tom Curran, Malay Haldar
bioRxiv 2020.02.12.945642; doi: https://doi.org/10.1101/2020.02.12.945642
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