High-resolution digital dissociation of brain tumors with deep multimodal autoencoder DOI Creative Commons

Jiao Sun,

Yue Pan, Tong Lin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract Single-cell technologies enable high-resolution, multi-dimensional analysis of molecular profiles in cancer biology but face challenges related to low coverage and cell annotation. The inherent hetero-geneity complexity brain tumors may hinder large-scale single multi-omic profiling. An efficient alternative is digital dissociation, which involves quantifying abundance purifying bulk samples at high resolution. However, most existing tools for resolving transcriptomes using scRNA-seq as a reference are not easily transferred other omics (e.g., chromatin accessibility, DNA methylation, protein) due ambiguous markers. Here, we introduce MODE, novel multimodal autoencoder neural network designed jointly recover personalized estimate cellular compositions. MODE the first algorithm trained on pseudo-bulk multi-omics derived from an external individualized non-RNA panel constructed target tumors. accuracy was evaluated through extensive simulation study, generated realistic data distinct tissue types. outperformed deconvolution pipelines with superior generalizability. Additionally, high-resolution purified by showed strong fidelity enhanced power detect differentially expressed genes. We applied methylome-transcriptome two independent tumor cohorts, revealing modality-specific landscapes pediatric medul-loblastoma (MB) adult glioblastoma (GBM). In MB tumors, accurately predicted composition embryonal lineage cells their marker genes expression. GBM, deconvoluted revealed increased myeloid associated poorer event-free survival. Overall, dissociation unravels origins, evolution, prognosis offering powerful tool state resolution without sequencing. pipeline freely available https://github.com/jsuncompubio/MODE .

Language: Английский

A spatially resolved single-cell genomic atlas of the adult human breast DOI
Tapsi Kumar, Kevin Nee, Runmin Wei

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7972), P. 181 - 191

Published: June 28, 2023

Language: Английский

Citations

124
Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues DOI Creative Commons
Huan Wang, Ruixu Huang,

Jack Nelson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 8, 2023

Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, gene signatures associated with pathological features, are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance three commercial iST on serial sections from tissue microarrays (TMAs) containing 23 tumor normal types both relative technical biological performance. On matched found that 10x Xenium shows higher transcript counts per without sacrificing specificity, but all concord to orthogonal RNA-seq datasets perform resolved cell typing, albeit different false discovery rates, segmentation error frequencies, varying degrees sub-clustering downstream analyses. Taken together, our analyses provide a comprehensive benchmark guide choice method as researchers design studies precious samples this rapidly evolving field.

Language: Английский

Citations

46
A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast DOI Creative Commons

Austin D. Reed,

Sara Pensa,

Adi Steif

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(4), P. 652 - 662

Published: March 28, 2024

Abstract Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk mastectomies. From more than 800,000 cells identified 41 subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according natural history tissue. Age, parity germline mutations, known modulate developing cancer, affected homeostatic cellular state in ways. We found BRCA1 BRCA2 carriers distinct gene expression signature indicative potential exhaustion, which was validated by immunohistochemistry. This suggests immune-escape mechanisms could manifest non-cancerous tissues very early during tumor initiation. is rich resource can be used inform novel approaches for detection prevention cancer.

Language: Английский

Citations

32
Metabolic switch regulates lineage plasticity and induces synthetic lethality in triple-negative breast cancer DOI Creative Commons
Yingsheng Zhang, Meng‐Ju Wu,

Wan-Chi Lu

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(1), P. 193 - 208.e8

Published: Jan. 1, 2024

Language: Английский

Citations

30
Implantation of engineered adipocytes suppresses tumor progression in cancer models DOI Creative Commons
Hai P. Nguyen,

Kelly An,

Yusuke Ito

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Tumors exhibit an increased ability to obtain and metabolize nutrients. Here, we implant engineered adipocytes that outcompete tumors for nutrients show they can substantially reduce cancer progression, a technology termed adipose manipulation transplantation (AMT). Adipocytes use amounts of glucose fatty acids by upregulating UCP1 were placed alongside cells or xenografts, leading significant suppression. Transplanting modulated organoids in pancreatic breast genetic mouse models suppressed their growth decreased angiogenesis hypoxia. Co-culturing patient-derived with tumor from dissected human cancers significantly progression proliferation. In addition, was impaired inducing using tetracycline placing them integrated cell-scaffold delivery platform implanting next the tumor. Finally, UPP1 uridine-dependent ductal adenocarcinoma uridine suppress its growth, demonstrating potential customization AMT.

Language: Английский

Citations

4
A cell atlas of the human fallopian tube throughout the menstrual cycle and menopause DOI Creative Commons
Melanie Weigert, Yan Li,

Lisha Zhu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 3, 2025

The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA ATAC sequencing to construct a comprehensive cell atlas of healthy human tubes Our scRNA-seq comparison 85,107 pre- 46,111 post-menopausal cells reveals substantial shifts in type frequencies, gene expression, transcription factor activity, cell-to-cell communications menopause cycle. Menstrual dependent hormonal regulate distinct states secretory epithelial cells. Postmenopausal show high chromatin accessibility factors associated with aging such as Jun, Fos, BACH1/2, while hormone receptors were generally downregulated, small proportion had expression ESR2, IGF1R, LEPR. While pre-menopausal cluster is enriched immunoreactive subtype, subset genes expressed enrichment mesenchymal high-grade serous ovarian cancer. cellular aging. Here, Weigert et al. present normal revealing transition throughout

Language: Английский

Citations

2
Preneoplastic stromal cells promote BRCA1-mediated breast tumorigenesis DOI
Kevin Nee, Dennis Ma, Quy H. Nguyen

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(4), P. 595 - 606

Published: March 13, 2023

Language: Английский

Citations

39
Label‐free single cell proteomics utilizing ultrafast LC and MS instrumentation: A valuable complementary technique to multiplexing DOI Creative Commons
Manuel Matzinger, Rupert L. Mayer, Karl Mechtler

et al.

PROTEOMICS, Journal Year: 2023, Volume and Issue: 23(13-14)

Published: Feb. 19, 2023

The ability to map a proteomic fingerprint transcriptomic data would master the understanding of how gene expression translates into actual phenotype. In contrast nucleic acid sequencing, in vitro protein amplification is impossible and no single cell workflow has been established as gold standard yet. Advances microfluidic sample preparation, multi-dimensional separation, sophisticated acquisition strategies, intelligent analysis algorithms have resulted major improvements successfully analyze such tiny amounts with steadily boosted performance. However, among broad variation published approaches, it commonly accepted that highest possible sensitivity, robustness, throughput are still most urgent needs for field. While many labs focused on multiplexing achieve these goals, label-free SCP highly promising strategy well whenever high dynamic range unbiased accurate quantification needed. We here focus recent advances single-cell mass spectrometry workflows try guide our readers choose best method or combinations methods their specific applications. further highlight which techniques propitious future applications but also limitations we foresee

Language: Английский

Citations

38
Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk DOI Creative Commons
Jason J. Northey, Mary-Kate Hayward, Yoshihiro Yui

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(1), P. 106 - 126.e13

Published: Jan. 1, 2024

Language: Английский

Citations

12
Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers DOI
Rachel Joyce, Rosa Pascual, Luuk Heitink

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 138 - 152

Published: Jan. 1, 2024

Language: Английский

Citations

11