小柯机器人

西班牙巴塞罗那科技学院Lars Velten和德国海德堡大学Carsten Müller-Tidow课题组合作，发现克隆分辨单细胞多组学鉴定急性髓性白血病(AML)细胞分化途径。这一研究成果于2023年4月24日发表在国际顶尖学术期刊《细胞—干细胞》上。

他们介绍了CloneTracer，这是一种新的方法，可以增加单细胞RNA-seq数据集的克隆分辨率。CloneTracer应用于19例AML患者的样本，揭示了白血病分化的途径。尽管剩余的健康细胞和白血病前期细胞主导了休眠干细胞室，但活跃的白血病干细胞(LSCs)与健康的LSCs相似，并保留了红细胞能力。相比之下，下游髓系祖细胞构成了一个高度异常的疾病定义室:它们的基因表达和分化状态既影响化疗反应，也影响白血病向转录正常单核细胞分化的能力。最后，他们证明了CloneTracer在识别白血病细胞中特异性失调的表面标记物方面的潜力。

综上所述，CloneTracer揭示了一种模仿其健康对应物的分化图景，并可能决定AML的生物学和治疗反应。

据了解，健康和LSC的患者间变异性和相似性阻碍了AML中LSCs的表征及其分化前景。

附：英文原文

Title: Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia

Author: Sergi Beneyto-Calabuig, Anne Kathrin Merbach, Jonas-Alexander Kniffka, Magdalena Antes, Chelsea Szu-Tu, Christian Rohde, Alexander Waclawiczek, Patrick Stelmach, Sarah Grle, Philip Pervan, Maike Janssen, Jonathan J.M. Landry, Vladimir Benes, Anna Jauch, Michaela Brough, Marcus Bauer, Birgit Besenbeck, Julia Felden, Sebastian Bumer, Michael Hundemer, Tim Sauer, Caroline Pabst, Claudia Wickenhauser, Linus Angenendt, Christoph Schliemann, Andreas Trumpp, Simon Haas, Michael Scherer, Simon Raffel, Carsten Müller-Tidow, Lars Velten

Issue&Volume: 2023-04-24

Abstract: Inter-patient variability and the similarity of healthy and leukemic stem cells (LSCs) have impeded the characterization of LSCs in acute myeloid leukemia (AML) and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. Although residual healthy and preleukemic cells dominated the dormant stem cell compartment, active LSCs resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors constituted a highly aberrant, disease-defining compartment: their gene expression and differentiation state affected both the chemotherapy response and leukemia’s ability to differentiate into transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers misregulated specifically in leukemic cells. Taken together, CloneTracer reveals a differentiation landscape that mimics its healthy counterpart and may determine biology and therapy response in AML.

DOI: 10.1016/j.stem.2023.04.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00119-4

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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