ECM Signatures Reveal Quiescent Stem Cell Diversity in the Colonic Niche DOI Open Access
Séamus Hickey, Massimo Andreatta,

Christina Enright

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

ABSTRACT Colonic stem cells have a key role in the continuous regeneration of healthy intestinal epithelium. Despite considerable advances single-cell omics technologies, transcriptional heterogeneity rare cell types such as colonic cells, well their functional states and niche-specific behaviors, remain poorly characterised. In this study, we leverage meta-analysis scRNA-seq spatial transcriptomic datasets to comprehensively map cells. We identify multiple, previously underappreciated states, including distinct quiescent subtypes marked by CDKN1A (P21), CDKN1B (P27), CDKN1C (P57), proliferative populations defined MKI67 (Ki67) LRIG1 , lineage-committed intermediate subpopulation expressing MUC2 . Strikingly, find that these can be robustly identified solely extracellular matrix (ECM) gene expression signatures, revealing ECM composition critical determinant identity. Notably, LAMA1 is highly specific P57+ population, linking laminin-mediated microenvironments active maintenance deep quiescence, consistent with our recent findings associating survival. By applying delineate discrete “micro-niches” tissue provide evidence analogous persist colorectal cancer (CRC) environment. Extending approach an unrelated tissue, pancreas, detect parallel subtypes, illustrating broader applicability ECM-based signatures. Taken together, redefine concept colon, establish ECM-driven signatures powerful tool for characterizing offer new perspectives on niche-dependent regulation both cancerous populations.

Language: Английский

ECM Signatures Reveal Quiescent Stem Cell Diversity in the Colonic Niche DOI Open Access
Séamus Hickey, Massimo Andreatta,

Christina Enright

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

ABSTRACT Colonic stem cells have a key role in the continuous regeneration of healthy intestinal epithelium. Despite considerable advances single-cell omics technologies, transcriptional heterogeneity rare cell types such as colonic cells, well their functional states and niche-specific behaviors, remain poorly characterised. In this study, we leverage meta-analysis scRNA-seq spatial transcriptomic datasets to comprehensively map cells. We identify multiple, previously underappreciated states, including distinct quiescent subtypes marked by CDKN1A (P21), CDKN1B (P27), CDKN1C (P57), proliferative populations defined MKI67 (Ki67) LRIG1 , lineage-committed intermediate subpopulation expressing MUC2 . Strikingly, find that these can be robustly identified solely extracellular matrix (ECM) gene expression signatures, revealing ECM composition critical determinant identity. Notably, LAMA1 is highly specific P57+ population, linking laminin-mediated microenvironments active maintenance deep quiescence, consistent with our recent findings associating survival. By applying delineate discrete “micro-niches” tissue provide evidence analogous persist colorectal cancer (CRC) environment. Extending approach an unrelated tissue, pancreas, detect parallel subtypes, illustrating broader applicability ECM-based signatures. Taken together, redefine concept colon, establish ECM-driven signatures powerful tool for characterizing offer new perspectives on niche-dependent regulation both cancerous populations.

Language: Английский

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