Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype

Evelyn S Hanemaaijer, Thanasis Margaritis, Karin Sanders, Frank L Bos, Tito Candelli, Hanin Al-Saati, Max M van Noesel, Friederike A G Meyer-Wentrup, Marc van de Wetering, Frank C P Holstege, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

33 Citations (Scopus)


Neuroblastoma is the most common extracranial solid tumor and accounts for ∼10% of pediatric cancer-related deaths. The exact cell of origin has yet to be elucidated, but it is generally accepted that neuroblastoma derives from the neural crest and should thus be considered an embryonal malignancy. About 50% of primary neuroblastoma tumors arise in the adrenal gland. Here, we present an atlas of the developing mouse adrenal gland at a single-cell level. Five main cell cluster groups (medulla, cortex, endothelial, stroma, and immune) make up the mouse adrenal gland during fetal development. The medulla group, which is of neural crest origin, is further divided into seven clusters. Of interest is the Schwann cell precursor ("SCP") and the "neuroblast" cluster, a highly cycling cluster that shares markers with sympathoblasts. The signature of the medullary SCP cluster differentiates neuroblastoma patients based on disease phenotype: The SCP signature score anticorrelates with ALK and MYCN expression, two indicators of poor prognosis. Furthermore, a high SCP signature score is associated with better overall survival rates. This study provides an insight into the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
Publication statusPublished - 02 Feb 2021


  • Adrenal Glands/pathology
  • Adrenal Medulla/pathology
  • Animals
  • Cell Aggregation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Inbred C57BL
  • Neoplasm Staging
  • Neural Stem Cells
  • Neuroblastoma/genetics
  • Phenotype
  • Schwann Cells/pathology
  • Single-Cell Analysis


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