TY - JOUR
T1 - Integrative spatial analysis reveals a multi-layered organization of glioblastoma
AU - Greenwald, Alissa C.
AU - Darnell, Noam Galili
AU - Hoefflin, Rouven
AU - Simkin, Dor
AU - Mount, Christopher W.
AU - Gonzalez Castro, L. Nicolas
AU - Harnik, Yotam
AU - Dumont, Sydney
AU - Hirsch, Dana
AU - Nomura, Masashi
AU - Talpir, Tom
AU - Kedmi, Merav
AU - Goliand, Inna
AU - Medici, Gioele
AU - Laffy, Julie
AU - Li, Baoguo
AU - Mangena, Vamsi
AU - Keren-Shaul, Hadas
AU - Weller, Michael
AU - Addadi, Yoseph
AU - Neidert, Marian C.
AU - Suvà, Mario L.
AU - Tirosh, Itay
PY - 2024/5/9
Y1 - 2024/5/9
N2 - Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all cancer cell states. Accordingly, tumor regions distant from any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.
AB - Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all cancer cell states. Accordingly, tumor regions distant from any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.
UR - http://www.scopus.com/inward/record.url?scp=85192155942&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2024.03.029
DO - 10.1016/j.cell.2024.03.029
M3 - Article
C2 - 38653236
AN - SCOPUS:85192155942
SN - 0092-8674
VL - 187
SP - 2485-2501.e26
JO - Cell
JF - Cell
IS - 10
ER -