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Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype [Developmental Biology]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2021-02-02 , DOI: 10.1073/pnas.2022350118
Evelyn S. Hanemaaijer 1 , Thanasis Margaritis 2 , Karin Sanders 1, 3 , Frank L. Bos 1 , Tito Candelli 2 , Hanin Al-Saati 1 , Max M. van Noesel 2 , Friederike A. G. Meyer-Wentrup 2 , Marc van de Wetering 1 , Frank C. P. Holstege 2 , Hans Clevers 1, 4
Affiliation  

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.



中文翻译:

发育中的小鼠肾上腺单细胞图谱揭示了雪旺氏细胞前体标志与神经母细胞瘤表型的关系[发育生物学]

神经母细胞瘤是最常见的颅外实体瘤,约占儿童癌症相关死亡的10%。确切的细胞来源尚待阐明,但通常认为神经母细胞瘤来自神经and,因此应被认为是胚胎恶性肿瘤。约50%的原发性神经母细胞瘤肿瘤发生在肾上腺。在这里,我们提出了单细胞水平上的发育中小鼠肾上腺的地图集。胎儿发育过程中,五个主要的细胞簇群(髓质,皮质,内皮,基质和免疫)组成了小鼠的肾上腺。起源于神经ull的延髓群又被分为七个簇。令人感兴趣的是雪旺氏细胞前体(“ SCP”)和“神经母细胞”簇,这是一个高度循环的簇,与交感神经母细胞共享标记。髓质SCP簇的特征可根据疾病表型区分成神经细胞瘤患者:SCP特征评分与预后不良的两个指标ALK和MYCN表达不相关。此外,较高的SCP签名得分与更好的整体生存率相关。这项研究提供了对正在发展的肾上腺的见解,并介绍了SCP基因标记,这对于进一步了解神经母细胞瘤表型感兴趣。

更新日期:2021-01-27
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