Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma
Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digit...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2024
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| Online Access: | https://hdl.handle.net/10356/174908 |
| _version_ | 1811685275058831360 |
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| author | Liu, Min Bertolazzi, Giorgio Sridhar, Shruti Lee, Rui Xue Jaynes, Patrick Mulder, Kevin Syn, Nicholas Hoppe, Michal Marek Fan, Shuangyi Peng, Yanfen Thng, Jocelyn Chua, Reiya Jayalakshmi Batumalai, Yogeshini De Mel, Sanjay Poon, Limei Chan, Esther Hian Li Lee, Joanne Hue, Susan Swee-Shan Chang, Sheng-Tsung Chuang, Shih-Sung Chandy, Kanianthara George Ye, Xiaofei Pan-Hammarström, Qiang Ginhoux, Florent Chee, Yen Lin Ng, Siok-Bian Tripodo, Claudio Jeyasekharan, Anand D. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Liu, Min Bertolazzi, Giorgio Sridhar, Shruti Lee, Rui Xue Jaynes, Patrick Mulder, Kevin Syn, Nicholas Hoppe, Michal Marek Fan, Shuangyi Peng, Yanfen Thng, Jocelyn Chua, Reiya Jayalakshmi Batumalai, Yogeshini De Mel, Sanjay Poon, Limei Chan, Esther Hian Li Lee, Joanne Hue, Susan Swee-Shan Chang, Sheng-Tsung Chuang, Shih-Sung Chandy, Kanianthara George Ye, Xiaofei Pan-Hammarström, Qiang Ginhoux, Florent Chee, Yen Lin Ng, Siok-Bian Tripodo, Claudio Jeyasekharan, Anand D. |
| author_sort | Liu, Min |
| collection | NTU |
| description | Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance. |
| first_indexed | 2024-10-01T04:41:56Z |
| format | Journal Article |
| id | ntu-10356/174908 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:41:56Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1749082024-04-21T15:41:15Z Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma Liu, Min Bertolazzi, Giorgio Sridhar, Shruti Lee, Rui Xue Jaynes, Patrick Mulder, Kevin Syn, Nicholas Hoppe, Michal Marek Fan, Shuangyi Peng, Yanfen Thng, Jocelyn Chua, Reiya Jayalakshmi Batumalai, Yogeshini De Mel, Sanjay Poon, Limei Chan, Esther Hian Li Lee, Joanne Hue, Susan Swee-Shan Chang, Sheng-Tsung Chuang, Shih-Sung Chandy, Kanianthara George Ye, Xiaofei Pan-Hammarström, Qiang Ginhoux, Florent Chee, Yen Lin Ng, Siok-Bian Tripodo, Claudio Jeyasekharan, Anand D. Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Cancer prognosis Cell heterogeneity Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance. Published version M.L. was supported by the China Scholarship Council (202006940018). A.D.J. was supported by the Singapore Ministry of Health’s National Medical Research Council Clinician Scientist Award (MOH-000715-00). Work in A.D.J.’s laboratory is funded by a core grant from the Cancer Science Institute of Singapore, National University of Singapore through the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative. The Genomic Variation in Diffuse Large B Cell Lymphomas study, from which the data presented in ref. 38 was derived, was supported by the Intramural Research Program of the National Cancer Institute, NIH, Department of Health and Human Services. CT was supported by the Italian Foundation for Cancer Research (AIRC) Investigator Grant IG ID.22145; 5 × 1000 Grant ID.22759, and the Italian Ministry of Education, University and Research (MIUR) Grant 2017K7FSYB. GB was supported by Italian Ministry of Education, University and Research (MIUR) through the “PON Research and Innovation 2014–2020”. 2024-04-16T01:42:46Z 2024-04-16T01:42:46Z 2024 Journal Article Liu, M., Bertolazzi, G., Sridhar, S., Lee, R. X., Jaynes, P., Mulder, K., Syn, N., Hoppe, M. M., Fan, S., Peng, Y., Thng, J., Chua, R., Jayalakshmi, Batumalai, Y., De Mel, S., Poon, L., Chan, E. H. L., Lee, J., Hue, S. S., ...Jeyasekharan, A. D. (2024). Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma. Nature Communications, 15(1), 2113-. https://dx.doi.org/10.1038/s41467-024-46220-z 2041-1723 https://hdl.handle.net/10356/174908 10.1038/s41467-024-46220-z 38459052 2-s2.0-85187165961 1 15 2113 en Nature Communications © The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Cancer prognosis Cell heterogeneity Liu, Min Bertolazzi, Giorgio Sridhar, Shruti Lee, Rui Xue Jaynes, Patrick Mulder, Kevin Syn, Nicholas Hoppe, Michal Marek Fan, Shuangyi Peng, Yanfen Thng, Jocelyn Chua, Reiya Jayalakshmi Batumalai, Yogeshini De Mel, Sanjay Poon, Limei Chan, Esther Hian Li Lee, Joanne Hue, Susan Swee-Shan Chang, Sheng-Tsung Chuang, Shih-Sung Chandy, Kanianthara George Ye, Xiaofei Pan-Hammarström, Qiang Ginhoux, Florent Chee, Yen Lin Ng, Siok-Bian Tripodo, Claudio Jeyasekharan, Anand D. Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma |
| title | Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma |
| title_full | Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma |
| title_fullStr | Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma |
| title_full_unstemmed | Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma |
| title_short | Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma |
| title_sort | spatially resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large b cell lymphoma |
| topic | Medicine, Health and Life Sciences Cancer prognosis Cell heterogeneity |
| url | https://hdl.handle.net/10356/174908 |
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