Tracking of donor and recipient immune and leukemia phenotypes after allogeneic stem cell transplantation using mitochondrial DNA mutations. [ASAP-Seq 1]

Mitochondrial DNA mutations (mtDNA) enable deconvolution of donor- and recipient-derived single cell profiles. Here, we provide examples for sensitive donor-recipient deconvolution of peripheral blood and bone marrow ASAP-seq profiles in the context of incipient and overt AML relapse following allogeneic hematopoietic stem cell transplantation. Further, using single cell DNA sequencing (Tapestri), we demonstrate co-evolution of mtDNA and somatic nuclear DNA mutations in relapsed CLL post-HSCT. Overall design: Staining of bone marrow or peripheral blood-derived single cells with oligotags for detection of surface marker expression using Total-seq A, B or D followed by single cell ATAC with select antigen profiling by sequencing (ASAP-seq) or single cell DNA sequencing using the Tapestri platform (Mission Bio).

线粒体DNA突变（mtDNA）可用于解卷积供体与受体来源的单细胞图谱。本数据集提供了异基因造血干细胞移植（Allogeneic Hematopoietic Stem Cell Transplantation, HSCT）后急性髓系白血病（Acute Myeloid Leukemia, AML）初发及显性复发背景下，对外周血与骨髓ASAP-seq图谱进行高灵敏度供体-受体解卷积的示例。进一步，本研究借助单细胞DNA测序（Tapestri），证实了异基因造血干细胞移植后复发的慢性淋巴细胞白血病（Chronic Lymphocytic Leukemia, CLL）中，mtDNA与体细胞核DNA突变的共同演化过程。实验整体设计：使用寡核苷酸标签对骨髓或外周血来源的单细胞进行染色，以通过Total-seq A、B或D检测表面标志物表达，随后开展测序联用选择性抗原谱分析的单细胞转座酶可及性测序（ASAP-seq），或使用Mission Bio公司的Tapestri平台进行单细胞DNA测序。