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Khven, I.

Publications and source records attributed to Khven, I..

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Sphingolipid Control of Fibroblast Heterogeneity Revealed by Single-Cell Lipidomics

Human cells produce thousands of lipids that impact a wide range of biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation events and also varies across individual cells of the same type. Yet, the precise differences in lipid composition that directly affect cell phenotypes remain unknown. Here we have measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We found that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in wound repair and in skin cancer growth. Sphingolipid composition defined fibroblast subpopulations while sphingolipid metabolic rewiring drove cell state transitions. These data uncover a role for cell-to-cell lipid heterogeneity in the determination of cell states and reveal a new regulatory component to the homeostasis and self-organization of multicellular systems.

biochemistry

Molecular architecture of the developing mouse brain

The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell-cell interactions, and intrinsic genetic programs that result in the generation of likely more than a thousand distinct cell types. Therefore, a complete understanding of mammalian brain development requires systematic mapping of cell states covering the entire relevant spatiotemporal range. Here we report a comprehensive single-cell transcriptome atlas of mouse brain development spanning from gastrulation to birth. We identified almost a thousand distinct cellular states, including the initial emergence of the neuroepithelium, a rich set of region-specific secondary organizers and a complete developmental program for the functional elements of the brain and its enclosing membranes. We used the atlas to directly test the hypothesis that human glioblastoma reflects a return to a developmental cell state. In agreement, most aneuploid tumor cells matched embryonic rather than adult types, while karyotypically normal cells predominantly matched adult immune cell types.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology