Αlpha¹ Record ID: 118FDFBD
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Lucarelli, D.; Parikh, S.; Jimenez, S.; Schneeweis, C.; Ngandiri, D. A.; Putze, P.; Kos, T.; Wellappili, D.; Goelling, V.; Kuerbanjiang et al.
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at advanced stages, yet single-cell datasets that capture late-stage and treated disease remain sparse, hindering progress in understanding tumour heterogeneity and therapy resistance. Here, we have generated integrated single-cell transcriptomic atlases of human and mouse PDAC to define the cellular and molecular landscape of the disease, from early to advanced and metastatic stages, including post-treatment disease, and to enable direct cross-species comparison. Using scANVI to harmonize 16 human studies comprising 257 donors and representative mouse models (101 tumours), we compiled over 1.6 million cells and established a four-level hierarchical taxonomy of more than 60 distinct cell states spanning malignant, stromal, immune, endothelial, adipose, exocrine and endocrine compartments. We resolve ten malignant programmes linked to progression and uncover rare immune phenotypes, including CD4CD8 double-positive T cells that remain poorly characterized in PDAC. Notably, we show that radiotherapy (RT) exposure is associated with enrichment of an EMT-persistent malignant state and an immunosuppressive microenvironment characterized by expansion of tumour-associated endothelium, depletion of intratumoral T cells and heightened laminin-CD44 signalling, with RT-associated genes linked to adverse prognosis in independent cohorts. Cross-species mapping reveals that orthotopic syngeneic allografts more faithfully recapitulate the cellular diversity and EMT-enriched states of advanced human PDAC, underrepresented in autochthonous genetically engineered models, with differences driven primarily by cell-type composition rather than pathway divergence. Together, these atlases and pretrained models provide a broadly accessible reference for benchmarking PDAC model fidelity and for interrogating mechanisms of tumour progression, microenvironmental remodelling and therapy response and resistance.
In a massive 1.6-million-cell nanoscale PDAC spy novel, human and mouse tumors swap notes on progression and radiotherapy's sneaky EMT-persistent villainy, with orthotopic models hilariously stealing the show as the most faithful mimics while rare double-positive T cells crash the immune party.
Shared by pancreatic cancer expert Anirban Maitra (@Aiims1742) calling it an "incredible resource" and computational biologist Fabian Theis (@fabian_theis) highlighting conserved core programs and model benchmarking; drew praise from the broader cancer and single-cell community for its therapy-resistance insights
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CD4⁺ T cells confer transplantable rejuvenation via Rivers of telomeres
Lanna, A.; Valvo, S.; Dustin, M.; Rinaldi, F.
Using a GPT-5-driven autonomous lab to optimize the cost and titer of cell-free protein synthesis
Smith, A. A.; Wong, E. L.; Donovan, R. C.; Chapman, B. A.; Harry, R.; Tirandazi, P.; Kanigowska, P.; Gendreau, E. A.; Dahl, R. H.; Jastrzebski, M.; Cortez, J. E.; Bremner, C. J.; Hemuda, J. C. M.; Dooner, J.; Graves, I.; Karandikar, R.; Lionetti, C.; Christopher, K.; Consiglio, A. L.; Tran, A.; McCusker, W.; Nguyen, D. X.; Nunes da Silva, I. B.; Bautista-Ayala, A. R.; McNerney, M. P.; Atkins, S.; McDuffie, M.; Serber, W.; Barber, B. P.; Thanongsinh, T.; Nesson, A.; Lama, B.; Nichols, B.; LaFrance, C.; Nyima, T.; Byrn, A.; Thornhill, R.; Cai, B.; Ayala-Valdez, L.; Wong, A.; Che, A. J.; Thavaraj
A Single-Cell and Spatial 3D Multi-omic Atlas of Developing Human Basal Ganglia and Inhibitory Neurons
Heffel, M. G.; Xu, H.; Pastor-Alonso, O.; Li, X.; Baig, M. S.; Irfan Ghoor, R.; Li, R.; Kern, C.; Kum, J.; Zhang, Y.; Paino, J.; Tsai, M. J.; Tai, C.-Y.; Tucker, G.; Zhao, Z.; Hou, A.; von Behren, Z.; Bhade, M.; Li, S.; Sandoval, K.; Scholes, J.; Codrea, F.; Calimlim, J.; Liao, E. K.; Leung, G.; Kim, J.; Eskin, E.; Flint, J.; Cotter, J. A.; Pasaniuc, B.; Bintu, B.; Zhu, Q.; Mukamel, E. A.; Ernst, J.; Paredes, M. F.; Luo, C.
Prediction of transformative breakthroughs in biomedical research
Davis, M. T.; Busse, B. L.; Arabi, S.; Meyer, P.; Hoppe, T. A.; Meseroll, R. A.; Hutchins, B. I.; Willis, K. A.; Santangelo, G. M.