Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas
Abstract Single-cell transcriptome profiling enables unparalleled characterization of the heterogeneous microenvironment of pediatric leukemias. To facilitate comparative analyses and generate pediatric leukemia signatures, we collect, process, and annotate single-cell data comprising over 540,000 c...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59362-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849314769851383808 |
|---|---|
| author | Hope L. Mumme Chenbin Huang Denis Ohlstrom Mojtaba Bakhtiari Sunil S. Raikar Deborah DeRyckere Muna Qayed Sharon M. Castellino Daniel S. Wechsler Christopher C. Porter Douglas K. Graham Swati S. Bhasin Manoj Bhasin |
| author_facet | Hope L. Mumme Chenbin Huang Denis Ohlstrom Mojtaba Bakhtiari Sunil S. Raikar Deborah DeRyckere Muna Qayed Sharon M. Castellino Daniel S. Wechsler Christopher C. Porter Douglas K. Graham Swati S. Bhasin Manoj Bhasin |
| author_sort | Hope L. Mumme |
| collection | DOAJ |
| description | Abstract Single-cell transcriptome profiling enables unparalleled characterization of the heterogeneous microenvironment of pediatric leukemias. To facilitate comparative analyses and generate pediatric leukemia signatures, we collect, process, and annotate single-cell data comprising over 540,000 cells from 159 different pediatric acute leukemia (myeloid, lymphoid, mixed phenotype lineages) and healthy bone marrow (BM) samples, profiled in our lab and curated from publicly available studies. The analysis identifies a leukemia-enriched signature of nine genes with over-expression in leukemic blast compared to healthy BM cells. This signature is also consistently over-expressed in leukemia samples compared to normal BM in bulk RNA-seq datasets (over 2000 samples). Outcome-based analysis on diagnosis samples using measurable residual disease (MRD) status depicts a significant association of oncogene-induced senescence and g-protein activation pathways with MRD positivity. MRD positivity across pediatric leukemias is also correlated with significant depletion of CD8+ and CD4+ naïve T-cells and M1-macrophages at diagnosis. To enable easy access to this comprehensive pediatric leukemia single-cell atlas, we develop the Pediatric Single-cell Cancer Atlas (PedSCAtlas, https://bhasinlab.bmi.emory.edu/PediatricSCAtlas/ ). The atlas allows for quick exploration of single-cell data based on genes, cell type composition, and clinical outcomes to understand the cellular landscape of pediatric leukemias. |
| format | Article |
| id | doaj-art-69ff25b719bf48608ceea0475aa564e7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-69ff25b719bf48608ceea0475aa564e72025-08-20T03:52:20ZengNature PortfolioNature Communications2041-17232025-05-0116111810.1038/s41467-025-59362-5Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlasHope L. Mumme0Chenbin Huang1Denis Ohlstrom2Mojtaba Bakhtiari3Sunil S. Raikar4Deborah DeRyckere5Muna Qayed6Sharon M. Castellino7Daniel S. Wechsler8Christopher C. Porter9Douglas K. Graham10Swati S. Bhasin11Manoj Bhasin12Department of Biomedical Informatics, Emory UniversityDepartment of Biomedical Informatics, Emory UniversityCoulter Department of Biomedical Engineering, Georgia Institute of TechnologyDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Pediatrics, Emory University School of MedicineDepartment of Biomedical Informatics, Emory UniversityAbstract Single-cell transcriptome profiling enables unparalleled characterization of the heterogeneous microenvironment of pediatric leukemias. To facilitate comparative analyses and generate pediatric leukemia signatures, we collect, process, and annotate single-cell data comprising over 540,000 cells from 159 different pediatric acute leukemia (myeloid, lymphoid, mixed phenotype lineages) and healthy bone marrow (BM) samples, profiled in our lab and curated from publicly available studies. The analysis identifies a leukemia-enriched signature of nine genes with over-expression in leukemic blast compared to healthy BM cells. This signature is also consistently over-expressed in leukemia samples compared to normal BM in bulk RNA-seq datasets (over 2000 samples). Outcome-based analysis on diagnosis samples using measurable residual disease (MRD) status depicts a significant association of oncogene-induced senescence and g-protein activation pathways with MRD positivity. MRD positivity across pediatric leukemias is also correlated with significant depletion of CD8+ and CD4+ naïve T-cells and M1-macrophages at diagnosis. To enable easy access to this comprehensive pediatric leukemia single-cell atlas, we develop the Pediatric Single-cell Cancer Atlas (PedSCAtlas, https://bhasinlab.bmi.emory.edu/PediatricSCAtlas/ ). The atlas allows for quick exploration of single-cell data based on genes, cell type composition, and clinical outcomes to understand the cellular landscape of pediatric leukemias.https://doi.org/10.1038/s41467-025-59362-5 |
| spellingShingle | Hope L. Mumme Chenbin Huang Denis Ohlstrom Mojtaba Bakhtiari Sunil S. Raikar Deborah DeRyckere Muna Qayed Sharon M. Castellino Daniel S. Wechsler Christopher C. Porter Douglas K. Graham Swati S. Bhasin Manoj Bhasin Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas Nature Communications |
| title | Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas |
| title_full | Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas |
| title_fullStr | Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas |
| title_full_unstemmed | Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas |
| title_short | Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas |
| title_sort | identification of leukemia enriched signature through the development of a comprehensive pediatric single cell atlas |
| url | https://doi.org/10.1038/s41467-025-59362-5 |
| work_keys_str_mv | AT hopelmumme identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT chenbinhuang identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT denisohlstrom identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT mojtababakhtiari identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT sunilsraikar identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT deborahderyckere identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT munaqayed identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT sharonmcastellino identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT danielswechsler identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT christophercporter identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT douglaskgraham identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT swatisbhasin identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas AT manojbhasin identificationofleukemiaenrichedsignaturethroughthedevelopmentofacomprehensivepediatricsinglecellatlas |