Abstract：
Fanconi anemia (FA) is the predominant hereditary syndrome of bone marrow failure (BMF), distinguished by impairments in DNA repair mechanisms. The deficiency in the FANC pathway, which governs DNA repair and replication rescue, results in aberrant responses to DNA damage in individuals with FA. The objective of this study is to examine the involvement of the FANC core complex in BMF and ascertain nucleolar homeostasis-related genes by conducting transcriptome analysis on primary hematopoietic stem cells obtained from FA patients with FANCA and FANCC variants. In the present study, we analyzed scRNA-seq data obtained from both healthy donors and individuals diagnosed with FA in order to investigate the phenomenon of cell-cell communication. Through the implementation of trajectory analysis, the differentiation pathways of several progenitor cell types, such as HSC cells transitioning into LMPP, N, M, B-prog, and E cells, were elucidated. Moreover, by scrutinizing the inferred interactions, notable disparities in cell-cell communication were observed between FA patients and their healthy counterparts. Our analysis has unveiled heightened interactions involving TNFSF13B, MIF, IL16, and COL4A2 in patients with FA. Furthermore, we have developed a prognostic model for predicting the outcome of acute myeloid leukemia (AML) which has exhibited remarkable predictive precision, with an AUC exceeding 0.83 at the 3- and 5-year intervals following the baseline assessment. In summary, the prognostic model that has been developed provides a valuable instrument for forecasting outcomes of AML by utilizing the genes identified through both single-cell and bulk transcriptome analyses.
摘要：
范可尼贫血（FA）是骨髓衰竭（BMF）的主要遗传性综合征，以DNA修复机制的损伤为特征。FANC途径的缺陷，控制DNA修复和复制拯救，导致FA个体对DNA损伤的异常反应。这项研究的目的是检查FANC核心复合物在BMF中的参与，并通过对从具有FANCA和FANCC变体的FA患者获得的原代造血干细胞进行转录组分析来确定核仁稳态相关基因。在本研究中,我们分析了从健康供体和诊断为FA的个体获得的scRNA-seq数据，以研究细胞-细胞通讯现象。通过实施轨迹分析,几种祖细胞类型的分化途径，例如HSC细胞转变为LMPP，N,M,B-prog,和E细胞，被阐明。此外，通过仔细检查推断的互动，在FA患者和健康者之间观察到细胞-细胞通讯的显著差异.我们的分析揭示了涉及TNFSF13B的相互作用增强，MIF,IL16和COL4A2在FA患者中的表达。此外，我们开发了一种预测急性髓系白血病（AML）预后的模型，该模型具有显著的预测精度，基线评估后3年和5年的AUC超过0.83。总之,已经开发的预后模型通过利用通过单细胞和批量转录组分析鉴定的基因,为预测AML结局提供了有价值的工具.
