---
title: "Spatial mapping links ADM–CALCRL and JAG1–NOTCH3 signaling to vascular niches in glioblastoma"
id: "biorxiv-4-petro-enables-robust-estimation-of-on-target-perturbation-effects-in-perturb-seq"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-petro-enables-robust-estimation-of-on-target-perturbation-effects-in-perturb-seq"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.15.759256v1?rss=1"
published_at: "2026-10-21T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Spatial mapping links ADM–CALCRL and JAG1–NOTCH3 signaling to vascular niches in glioblastoma
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-petro-enables-robust-estimation-of-on-target-perturbation-effects-in-perturb-seq
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.15.759256v1?rss=1)
- **Published At:** 2026-10-21T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The figure analyzes tumor:vascular interactions in **glioblastoma**, using spatial assays (Xenium and RNAscope) to map ligand-receptor relationships across tumor niches. - Investigators defined tumor sender states (Hypoxic: S2 or S4; Stem-like: S1 or S5) and examined myeloid, neuronal/glial, and vascular cell receivers. - The **ADM:CALCRL** ligand-receptor pair was assessed across sender-receiver pairs; unique pairs were highlighted in the analysis. - An interaction network displays the frequency (color and arrow density) with which ADM:CALCRL was detected as significant across samples for specific sender-receiver pairings. - A heatmap shows per-cell-type expression of **ADM** and **CALCRL** stratified by niche. - Expression by tumor-region localization was queried using IVY-GAP data; the source reported that localization-based expression differences were examined. - Bar plots summarize the percent of **ADM**+ cells among **SOX2**+ tumor cells and percent of **CALCRL**+ among **PECAM1**+ vascular cells across samples (n=5). - Median per-sample distances were computed from **ADM**+ **SOX2**+ tumor cells to the nearest **CALCRL**- or **CALCRL**+ **PECAM1**+ cells; results are shown as sample-level bar plots. - Parallel analyses evaluated **JAG1** expression in **SOX2**+ tumor cells and **NOTCH3** in **PDGFRB**+ or **PECAM1**+ stromal cells, including median nearest-neighbor distances between **JAG1**+ tumor cells and **NOTCH3**- or **NOTCH3**+ PDGFRB+ cells. - The figure aggregates spatial ligand-receptor detection, expression heatmaps, IVY-GAP localization data, percentage-positive cell counts, and median distance metrics; the source did not report detailed numerical values beyond sample count (n=5), nor did it provide statistical test descriptions or p-values in the figure legend.
## Clinical Analysis & Structured Key Points
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Khan, Anthony Z. Wang, Rupen R. Desai, Gyeong Dae Kim, Colin R. McCornack, Rui Sun, Sonika M. Dahiya, Jennifer A. Foltz, Ngima D. Sherpa, Katherine Xu, Harrison Olszewski, Markus Anzaldua-Campos, Yuhui Song, Elizabeth Seider, Natan Pirete Gadens, Jose Maldonado, Lydia Leavitt, Timothy West, Alexander F. Wang, Bryan D. Choi, Eric C. Leuthardt, Bhuvic Patel, Kathleen Pfaff, Linda Nieman, Aleksandar Krbanjevic, Al Charest, Albert H. Kim, Gavin P. Dunn, Allegra A. Petti DOI: 10.1101/2025.04.04.647096 Published 1 January 2026 Saad M. Khan 1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 2Brain Tumor Immunology and Immunotherapy Program, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Saad%2BM.%2BKhan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Khan%20SM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASaad%2BM.%2BKhan%2B) Anthony Z. Wang 1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 2Brain Tumor Immunology and Immunotherapy Program, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 3Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anthony%2BZ.%2BWang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Wang%20AZ&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnthony%2BZ.%2BWang%2B) Rupen R. 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Sherpa 1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 2Brain Tumor Immunology and Immunotherapy Program, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 9Biological and Biomedical Sciences Graduate Program, Harvard University, Cambridge, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ngima%2BD.%2BSherpa%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sherpa%20ND&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANgima%2BD.%2BSherpa%2B) Katherine Xu 10Mass General Brigham Cancer Institute, Krantz Family Center for Cancer Research, Boston, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Katherine%2BXu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Xu%20K&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKatherine%2BXu%2B) Harrison Olszewski 11Dana Farber Cancer Institute Center for Immuno-Oncology, Boston, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Harrison%2BOlszewski%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Olszewski%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHarrison%2BOlszewski%2B) Markus Anzaldua-Campos 5Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Markus%2BAnzaldua-Campos%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Anzaldua-Campos%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMarkus%2BAnzaldua-Campos%2B) Yuhui Song 10Mass General Brigham Cancer Institute, Krantz Family Center for Cancer Research, Boston, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yuhui%2BSong%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Song%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYuhui%2BSong%2B) Elizabeth Seider 10Mass General Brigham Cancer Institute, Krantz Family Center for Cancer Research, Boston, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Elizabeth%2BSeider%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Seider%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AElizabeth%2BSeider%2B) Natan Pirete Gadens 12The Broad Institute of MIT and Harvard, Cambridge, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Natan%2BPirete%2BGadens%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Gadens%20NP&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANatan%2BPirete%2BGadens%2B) Jose Maldonado 1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 2Brain Tumor Immunology and Immunotherapy Program, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 9Biological and Biomedical Sciences Graduate Program, Harvard University, Cambridge, MA, USA * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jose%2BMaldonado%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Maldonado%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJose%2BMaldonado%2B) Lydia Leavitt 13Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 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