Biology subjects

Angus-Hill, M. L.

Publications and source records attributed to Angus-Hill, M. L..

3 recordsLinked to original sources

bioRxiv2026

Multi-omic profiling of human antibody-secreting cells reveals diverse subsets sustain durable humoral immunity

Antibody-secreting cells (ASCs) provide humoral immunity that can mediate lifelong protection against pathogens. Current classifications cannot delineate the heterogenous functionalities, tissue residencies, and lifespans of human ASC subsets, impeding clinical translation. We applied multi-omic sequencing, spatial proteomics, and functional assays to discover and characterize human bone marrow (BM) ASC subsets. We identified two peripheral subsets (ASCp) also present in blood and three BM-resident subsets (ASCr), comprising a maturation continuum associated with increased mitochondrial networking, diminished antibody secretion, differential transcription factor motif accessibility, and preferential co-localization in homotypic niches. CD19+9+ASCr and CD19-ASCr exhibited poor recovery years after BM transplantation, indicating a strong dependence on supportive niches. Childhood vaccine antigens were recognized by long-lived ASCr subsets in adults and by immature HLA-DR+ASCp, implying ASCs can differentiate without recent antigen exposure. Our results provide new insights into ASC identity, maturation, and longevity and a generalizable framework for study and manipulation of human ASCs.

immunology↗

bioRxiv2026

A Rare T-Cell Factor 4 Lineage-negative Epithelial Stem Cell Supports Wound Repair and APC-deletion-induced Colon Tumorigenesis

To maintain barrier homeostasis, the colonic and intestinal epithelial lining is continually renewed by rapidly proliferating epithelial crypt base columnar (CBC) stem cells that reside at the base of crypts. Using mouse lineage tracing, immunohistochemistry, and single-cell sequencing, we have identified a rare, non-CBC, T-cell factor 4 lineage-negative (Tcf4 Lin-) stem cell population that gives rise to secretory and absorptive precursors. Following endoscopic biopsy-induced injury, Tcf4 Lin- stem cells are recruited to the wound bed and to the site of expanding crypts and function in barrier restoration and wound repair. We show that in a Tcf4-haploinsufficient background, the Tcf4 Lin-, but not the Tcf4 Lin+, cell population represents the cell of origin for colon tumors driven by deletion of Apc. Our results provide a foundation for understanding Apc-allele-specific differences during colon tumorigenesis and identify a new stem-cell population that may prove valuable in the treatment of diseases caused by intestinal barrier homeostasis defects.

cell biology↗

bioRxiv2025

Dissecting type I and II interferon impacts on human immune cells in disease by a cell type-specific interferon response atlas

Interferons (IFNs) orchestrate diverse immune responses, but distinguishing individual IFN contributions in human transcriptomic data is challenging due to overlapping interferon-stimulated gene (ISG) signatures and limited cell-type-specific datasets. To address this, we generated a single-cell transcriptomic atlas of IFN responses by stimulating primary human T, B, NK, and CD14 monocytes with IFN-I, IFN-II, and IFN-III. This revealed core and cell-type-specific ISG programs across 13 subsets, highlighting distinct functions of IFNs. We developed an algorithm to separate IFN-I and IFN-II activity in transcriptomic data. Applied to multiple myeloma samples, it showed elevated IFN-I and IFN-II responses, with induction therapy reducing only IFN-I. Extending to multiple disease datasets provided a cross-disease overview of IFN-I and IFN-II activities and revealed increased IFN-II activities in T cells during lupus flares. This resource and the accompanying analytical framework enable dissection of IFN-driven transcriptional programs in a cell-type specific manner in human disease.

immunology↗