MITF-low melanoma subtype models in zebrafish reveal transcriptional sub-clusters and MITF-independent residual disease. MITF-low melanoma subtype models in zebrafish reveal transcriptional sub-clusters and MITF-independent residual disease

The MITF-low melanoma transcriptional signature is predictive of poor outcome for patients but little is known about its biological signature. We used genetic models of zebrafish with low expression of mitfa (MITF-low) to study this biological subtype. Using genetic inhibition of MITF activity we discover minimal residual disease at the site of regression. We performed single cell RNA-seq (Smart-seq2) to characterise cells at the site of residual disease, and put in relation with primary tumours and recurring disease. Overall design: We performed single cell RNAseq experiment (Smart-seq2) of zebrafish primary superficial and nodular melanomas, corresponding residual diseases and beginning of recurrence (nodular melanoma only).

MITF低表达黑色素瘤转录特征（MITF-low melanoma transcriptional signature）可有效预测患者的不良预后，但目前对其生物学特征的认知仍较为有限。我们利用mitfa低表达（MITF-low）的斑马鱼遗传模型研究该黑色素瘤生物学亚型。通过遗传抑制MITF的活性，我们在肿瘤消退位点发现了微量残留病灶。我们采用单细胞RNA测序（single cell RNA-seq，Smart-seq2）技术对残留病灶部位的细胞进行表征，并将其与原发性肿瘤及复发病例进行关联分析。实验整体设计：我们对斑马鱼原发性浅表性黑色素瘤、结节性黑色素瘤、对应部位的残留病灶以及复发初期（仅针对结节性黑色素瘤）的样本开展了单细胞RNA测序（Smart-seq2）实验。