Inferring cell lineage differential gene expression analysis using singlecell RNA-seq

Backgrounds: Single-cell RNA sequencing (scRNA-seq) analysis can investigate geneexpression at single-cell resolution and track the trajectories of distinct cell lineages. Intra-tumorheterogeneity (ITH) includes cellular differences in tumors and is associated with clinicaloutcomes such as drug resistance. Expression profiling of cells individually allows monitoringITH and may unravel the dynamics of specific sub-population of tumoral cells. To identifydifferentially expressed genes in different lineages of Acute Lymphoblastic Leukemia (ALL), weutilized a scRNA approach to scrutinize the ETV۶-RUNX role in promoting tumorigenesis.Materials and Methods: We used the Seurat R package to analyze ۳۰۹۴ Pre-B t (۱۲;۲۱) [ETV۶-RUNX۱] ALL cells sequenced by ۱۰x Genomics' scRNA-seq technology. Raw data retrievedfrom SRA public database (SRR۹۲۶۴۳۴۳) and was processed to obtain count matrices usingCellranger count tools. UMAP algorithm and Slingshot was applied for dimensionality reductionand identifying branch-specific changes in gene expression respectively.Results: We found ۹ clusters and ۲ lineages in our data. ۱۲ genes were differentially expressedbetween ۲ lineages, including TERF۲, ID۳, XRCC۶, ATF۴, and DDX۱۷. We focused on ID۳and its biological networks. Our data not only showed a significant aberrant pattern of cellularheterogeneity between normal and tumoral cells but also ETV۶-RUNX is intriguingly showed adistinguished cellular signature.Conclusion: Based on our findings ID۳ may be considered as a critical marker in ETV۶-RUNXharboring cells. Its crucial biological roles in cell cycle, regulation of DNA replication andregulation of cell differentiation, may pave the way for generating of a new subtype of cells andshould be considered as one of the key genes related to evolvability of lymphoblastic progenitorsin ALL.

کلیدواژه ها:

scRNA-seq ، Acute Lymphoblastic Leukemia (ALL) ، ID۳ ، ETV۶-RUNX۱ ، Intratumor heterogeneity