Cajal-Retzius cells are critical in cortical lamination, but very little is known about their origin and development. The homeodomain transcription factor Dbx1 is expressed in restricted progenitor domains of the developing pallium: the ventral pallium (VP) and the septum. Using genetic tracing and ablation experiments in mice, we show that two subpopulations of Reelin(+) Cajal-Retzius cells are generated from Dbx1-expressing progenitors. VP- and septum-derived Reelin(+) neurons differ in their onset of appearance, migration routes, destination and expression of molecular markers. Together with reported data supporting the generation of Reelin(+) cells in the cortical hem, our results show that Cajal-Retzius cells are generated at least at three focal sites at the borders of the developing pallium and are redistributed by tangential migration. Our data also strongly suggest that distinct Cajal-Retzius subtypes exist and that their presence in different territories of the developing cortex might contribute to region-specific properties.

Highlights d Distinct CD8 + T cell phenotypes are enriched after immune checkpoint blockade (ICB) d Immune checkpoint ligands are upregulated in macrophages and tumor cells after ICB d Two cancer cell subpopulations are conserved across heterogeneous RCC tumors d Cancer cell programs drive distinct immune interactions and predict patient outcomes

Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis 1 . To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA-seq (scRNA-seq) to profile ~11,000 cells from 22 ascites specimens from 11 HGSOC patients. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We find that the previously described "immunoreactive" and "mesenchymal" subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells 2 . Malignant cell variability was partly explained by heterogeneous copy number alterations (CNA) patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in scRNA-seq of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient-ascites-derived xenograft models. Inhibition of the JAK/STAT-pathway, which was expressed in both malignant cells and CAFs, had potent anti-tumor activity in primary short-term cultures and PDX models. Our work contributes to resolving the HSGOC landscape 3-5 and provides a resource for the development of novel therapeutic approaches.