Biology subjects

Eriksson, C.-J.

Publications and source records attributed to Eriksson, C.-J..

4 recordsLinked to original sources

bioRxiv2025

Cell lineage inference from mitochondrial mutations

Tracing genealogical relationships between cells and their molecular states is essential for understanding tissue development, maintenance and disease. We present mt-SCITE, a computational method that reconstructs cell division histories from mitochondrial mutations in single cells. On simulated and experimental benchmarks, mt-SCITE outperformed existing methods in terms of cell lineage reconstruction, and scaled to thousands of cells. Applied to expanded CD8+ T cells following vaccination, mt-SCITE resolved subclonal relationships and revealed clones with predominantly memory-like, effector-like, or mixed states. mt-SCITE robustly identifies clonally related populations and resolves substructure within them, providing a broadly applicable approach to study cell lineage development.

bioinformatics↗

bioRxiv2023

Cytomegalovirus promotes proliferation and survival of prostate cancer cells and constitutes a therapeutic target

Metastatic prostate cancer is incurable and new therapeutic targets and drugs are needed. Viruses are associated with several cancer types, but their connection to prostate cancer is unclear. Here we show that human herpes virus cytomegalovirus (CMV) infection is common in the healthy prostate epithelium as well as in prostate cancer, with 85% of tumors being infected to varying degrees. The CMV gene locus UL122-UL123 upheld viral genome persistence in endogenously CMV infected prostate cancer cell lines. CMV promoted prostate cancer cell viability independently of androgen receptor status and anti-androgen resistance, partly through CMV UL97 and the androgen signaling pathway. DNA intercalation mitigated CMV infection and reduced CMV-dependent tumor size in xenotransplantation experiments. The anti-herpes drug aciclovir showed modest effects, but the well tolerated CMV UL97 kinase inhibitor maribavir partly mimicked CMV loss by inducing apoptosis and attenuating proliferation, resulting in reduced tumor growth in vivo. We conclude that CMV infects prostate cells in vivo and alters core prostate cancer cell properties, suggesting that it can be therapeutically targeted to improve prostate cancer outcomes.

cancer biology↗

bioRxiv2022

Clonally heritable gene expression imparts a layer of diversity within cell types

Cell types can be classified based on shared patterns of transcription. Variability in gene expression between individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. We asked whether long-term, heritable differences in transcription can impart diversity within a cell type. Studying clonal human lymphocytes and mouse brain cells, we uncover a vast diversity of heritable transcriptional states among different clones of cells of the same type in vivo. In lymphocytes we show that this diversity is coupled to clone specific chromatin accessibility, resulting in distinct expression of genes by different clones. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging and disease.

systems biology↗

bioRxiv2019

Clonally distinct differentiation trajectories shape CD8+ memory T cell heterogeneity after acute viral infections in humans

CD8+ T cells play essential roles in immunity to viral and bacterial infections, and to guard against malignant cells. The CD8+ T cell response to an antigen is composed of many T cell clones with unique T cell receptors, together forming a heterogenous repertoire of phenotypically and functionally distinct effector and memory cells1, 2. How individual T cell clones contribute to this heterogeneity during an immune response is key to understand immunity but remains largely unknown. Here, we longitudinally tracked CD8+ T cell clones expanding in response to yellow fever virus vaccination at the single cell level in humans. We show that only a fraction of the clones detected in the acute response persists as circulating memory T cells, indicative of clonal selection. Clones persisting in the memory phase displayed biased differentiation trajectories along a gradient of stem cell memory (SCM) towards terminally differentiated effector memory (EMRA) fates. Reactivation of single memory CD8+ T cells revealed that they were poised to recapitulate skewed differentiation trajectories in secondary responses, and this was generalizable across individuals for both yellow fever and influenza virus. Together, we show that the sum of distinct clonal differentiation repertoires results in the multifaceted T cell response to acute viral infections in humans.

immunology↗