Single cell RNA seq of the developing murine adrenal gland reveals correlation of Schwann cell precursor signature to neuroblastoma phenotype.

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 anti- correlates 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 in the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype. Sequencing of adrenal gland single cells in duplicate for embryonic days 13.5, 14.5, 17.5, 18.5 and postnatal days 1 and 5神经母细胞瘤（Neuroblastoma）是最常见的颅外实体瘤，约占儿童癌症相关死亡病例的10%。其确切的细胞起源尚未阐明，但学界普遍认为神经母细胞瘤源自神经嵴，因此应被归类为胚胎源性恶性肿瘤。约50%的原发性神经母细胞瘤发生于肾上腺。本研究呈现了发育中小鼠肾上腺的单细胞图谱。胎儿发育阶段的小鼠肾上腺由五大主要细胞簇群组成：髓质、皮质、内皮、基质及免疫细胞。其中源自神经嵴的髓质簇群可进一步细分为七个亚簇。值得关注的是施万细胞前体（Schwann cell precursor, SCP）簇与神经母细胞簇——后者是一类高增殖活性的亚簇，与交感神经母细胞共享标志物。髓质SCP簇的基因特征可依据疾病表型区分神经母细胞瘤患者：SCP特征评分与ALK和MYCN的表达呈负相关，而二者均为不良预后指标。此外，较高的SCP特征评分与更优的总生存率相关。本研究为发育中的肾上腺提供了全新见解，并提出SCP基因特征可作为进一步解析神经母细胞瘤表型的研究靶点。本研究对胚胎第13.5、14.5、17.5、18.5天以及出生后第1、5天的小鼠肾上腺单细胞进行了重复测序。