Single cell transcriptional profiling identifies heterogeneity in
pleuropulmonary blastoma
Abstract
Background: Pleuropulmonary blastoma (PPB) is a rare lung malignancy in
children derived from mesenchyme. Single-cell RNA sequencing is used to
explore the heterogeneity of tumors. Here, we used this technology to
classify PPB subpopulations and predict their differentiation
trajectory. Procedure: This study included 10 007 single cells from a
girl with PPB. After choosing malignant tumor cells with an inferring
copy number variation, we used non-negative matrix factorization and
Seurat analysis to cluster the cells and divided the subgroups by their
differentially expressed genes and Gene Ontology enrichment analysis.
Additionally, pseudotime trajectory analysis of PPB was conducted with
Monocle. Results: Tumor cells were divided into two major categories
including muscle (DEShiTNNT1hiTNNI1hi) and cartilage
(TWIST1hiHTRA1hiBMP4hi). In muscle lineage, satellite myogenic cells
(PAX7hiMYF5hiMSChi), which were subdivided into more primitive FABP7hi
one and later ITM2Ahi one, were the origin of muscle in PPB and
gradually differentiated into myocytes (MYOGhiTTNhiMYL4hi). And in the
cartilage lineage, SOX9hiPAX1hiPAX9hi prechondrocytes generated
MGPhiOGNhi chondrocytes and DKK2hiTNMDhi chondrocytes. Conclusions: Our
results demonstrated unrecognized heterogeneity in PPB at the single
cell level and defined its muscle and cartilage subpopulations together
with their trajectories, which would provide some basis for the
molecular mechanism and treatment of PPB.