TY - JOUR
T1 - Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype
AU - Hanemaaijer, Evelyn S
AU - Margaritis, Thanasis
AU - Sanders, Karin
AU - Bos, Frank L
AU - Candelli, Tito
AU - Al-Saati, Hanin
AU - van Noesel, Max
AU - Meyer-Wentrup, Friederike A G
AU - van de Wetering, Marc
AU - Holstege, Frank C P
AU - Clevers, Hans
N1 - Copyright © 2021 the Author(s). Published by PNAS.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Adrenal Glands/pathology
KW - Adrenal Medulla/pathology
KW - Animals
KW - Cell Aggregation
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Mice, Inbred C57BL
KW - Neoplasm Staging
KW - Neural Stem Cells
KW - Neuroblastoma/genetics
KW - Phenotype
KW - Schwann Cells/pathology
KW - Single-Cell Analysis
UR - http://www.scopus.com/inward/record.url?scp=85100001014&partnerID=8YFLogxK
U2 - 10.1073/pnas.2022350118
DO - 10.1073/pnas.2022350118
M3 - Article
C2 - 33500353
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
M1 - e2022350118
ER -