Project description:Purpose: To characterize heterogeneity of GSI-responsive and -resistant T-ALL cells Method: We generated GSI-resistant T-ALL DND41 cells and profiled their transcriptome using single-cell RNA sequencing. Result: We report here the presence of resistant-like subpopulation in drug naïve DND41 T-ALL cells. Conclusion: While other popular scRNA-seq clustering algorithms failed, TooManyCells, a suite of clustering and visualization algorithm developed in our lab, could identify rare resistant-like DND41 T-ALL cells.
Project description:Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors (TFs) in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterised by distinctive TF expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated TF pairings, including previously unrecognised relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a novel regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease. Examination of Gata2 and Gfi1 binding patterns in murine mast cells
Project description:Single-Cell Chromatin Analysis of Mammary Gland Development Reveals Cell-State Transcriptional Regulators and Lineage Relationships
Project description:Bilaterian animals display a wide variety of cell types, organized into defined anatomical structures and organ systems, which are mostly absent in pre-bilaterian animals. Xenacoelomorpha are an early branching bilaterian phylum displaying an apparently relatively simple anatomical organization that have greatly diverged from other Bilaterian clades. In this study, we use whole-body single-cell transcriptomics on the acoel Isodiametra pulchra to identify and characterize different cell types. Our analysis identifies the existence of at least 11 major cell-type categories in acoels all contributing to the main biological functions of the organism: metabolism, locomotion and movements, behavior, defense and development. Interestingly, while most cell clusters express core fate markers shared with other animal clades, we also describe a surprisingly large numbers of clade-specific marker genes, suggesting the emergence of clade-specific common molecular machineries functioning in distinct cell types. Together, these results provide novel insight into the evolution of bilaterian cell-types and open the door to a better understanding of the origins of the bilaterian body plan and their constitutive cell types.