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OCI-AML22 multiome datasets (scRNA-Seq/scATAC-Seq)

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272187 | GEO | 2024/10/02

REPOSITORIES: GEO

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