Project description:The leukemia stem cell (LSC) compartment is a complex reservoir fuelling disease progression in acute myeloid leukemia (AML). The existence of heterogeneity within this compartment is well documented but prior studies have focused on genetic heterogeneity without being able to address functional heterogeneity. Understanding this heterogeneity is critical for the informed design of therapies targeting LSC, but has been hampered by LSC scarcity and the lack of reliable cell surface markers for viable LSC isolation. To overcome these challenges, we turned to the patient-derived OCI-AML22 cell model. This model includes functionally, transcriptionally and epigenetically characterized LSC broadly representative of LSC found in primary AML samples. Focusing on the pool of functionally assessed LSC (Boutzen et al, Leukemia, 2022), we performed single cell RNA-Seq/ATAC-Seq analysis. Using an integrated approach combining xenograft assays this single-cell analysis identified two LSC subtypes with distinct transcriptional, epigenetic and functional properties. These LSC subtypes differed in depth of quiescence, differentiation potential, repopulation capacity, sensitivity to chemotherapy and could be isolated based on CD112 expression. A majority of AML patient samples had transcriptional signatures reflective of either LSC subtype, and some even showed coexistence within an individual sample.
Project description:Here, we performed multiome sequencing (snRNA-seq + snATAC-seq) of human fetal liver samples from 3 trisomy 21 (Ts21) and 3 healthy foetuses (median age 14 post-conception weeks). The data set is composed of approximately 60,000 CD45+ foetal liver cells.
Project description:To investigate how SHH treatment influences patterning of early brain organoids, we performed multiome sequencing of brain organoids during early development
Project description:This study generated multiome profiling of scRNA-seq and scATAC-seq data from ∼11,000 differentiating mouse embryonic stem cells over a time course. It demonstrates scTIE achieves effective data integration while preserving more biological signals than existing integration methods.
Project description:Aging is a universal biological phenomenon linked to many diseases, such as cancer or neurodegeneration. However, the molecular mechanisms underlying aging, or how lifestyle interventions such as cognitive stimulation can ameliorate this process, are yet to be clarified. Here, we performed a multi-omic profiling, including RNA-seq, ATAC-seq, ChIP-seq, EM-seq, SWATH-MS and single cell Multiome scRNA and scATAC-seq, in the dorsal hippocampus of young and old mouse subjects which were subject to cognitive stimulation using the paradigm of environmental enrichment. In this study we were able to describe the epigenomic landscape of aging and cognitive stimulation.
Project description:Plasmodium-specific CD4+ T cells from mice infected with Plasmodium chabaudi chabaudi AS parasites were recovered at Days 0, 4, 7, and 32 to undergo processing and to generate scATAC-seq dataset. At Day 7, CXCR5+ and CXCR6+ cells were recovered separately. At Day 32, mice were administered with either saline or artesunate (intermittent artesunate therapy - IAT). scATAC-seq dataset was analysed to investigate epigenomic landscapes of CD4+ T cells from effector to memory states.