Biology subjects

Kimler, K.

Publications and source records attributed to Kimler, K..

5 recordsLinked to original sources

bioRxiv2026

The Human Gut Cell Atlas v1.0: A Unified, Community-BuiltReference of Cellular Diversity Across the Gut

Single-cell RNA-sequencing (scRNA-seq) studies have transformed our understanding of cellular diversity in the human intestine, but differences in anatomical sampling, experimental processing and cell-type nomenclature limit comparison across datasets. Here, we present the Human Gut Cell Atlas (HGCA) V1, a community-curated reference of 944,390 healthy and disease-adjacent intestinal cells from 502 samples, 265 donors and 24 landmark studies, linked to detailed anatomical, clinical, and technical metadata. As this metadata is of critical importance to human biology, we developed MetaManager, an open source data management framework for standardized metadata collection and tracking. A five-level consensus taxonomy resolves 94 homeostatic cell identities and enables transferrable, high-resolution annotation of new gut datasets. By assembling cell identity, sampling metadata, and independent spatial validation, intestinal segment and radial tissue depth were revealed to systematically shape cellular composition and transcriptional state, enabling inference of the presence of sampling-dependent tissue niches, including lymphoid follicles. Reference mapping accurately and rapidly recovered cohort-level Crohn's disease and treatment signatures without de novo annotation, while mapping human intestinal organoids quantified cell-type-specific identity, regional specification, maturation, and transcriptional fidelity to native tissue. The HGCA V1 provides a standardized cellular, anatomical coordinate, and metadata system for reproducible, high-quality analysis of intestinal biology across healthy tissue, disease-associated remodelling, and experimental models, providing a continuously evolving community reference for cumulative discovery in human intestinal biology.

systems biology↗

bioRxiv2026

A Community-Driven Single-Cell PBMC Reference Integrating Landmark Datasets Spanning Health and Disease

Blood provides an accessible window into human health, yet the absence of a peripheral blood mononuclear cells (PBMCs) reference with standardized immune cell annotations has constrained comparisons between single-cell RNA sequencing (scRNAseq) studies. Here, we present HARP (Human Cell Atlas Reference for PBMCs), an integrated atlas of ~9 million PBMCs from >2,600 donors across 15 studies spanning four continents, encompassing diverse populations, neonates to 97 years, across health and diverse immune-related diseases. We developed optimized integration workflows, including novel label-free metrics to assess integration quality, and generated community-driven consensus annotations for 192 immune cell subsets, identifying rare populations representing as few as 0.004% of PBMCs. HARP reveals coordinated cellular modules associated with age, sex, and disease, identifies female-biased interferon and inflammatory gene programs and their perturbation by COVID-19, and uncovers a novel sexual dimorphism in prostaglandin signaling. Finally, we introduce scTiger, a hierarchical label-transfer framework that accurately projects these 192 cell annotations onto ~18 million additional PBMCs, providing a robust and transferable reference for harmonizing future PBMC studies. HARP provides a high-resolution community-driven reference atlas for PBMC annotation and analysis, as a basis for emerging clinical applications of single-cell genomics.

immunology↗

bioRxiv2026

Unique nasal cell states induced by common pediatric respiratory viruses

Respiratory viral infections in early childhood are major drivers of acute morbidity and long-term airway disease, yet how distinct viruses remodel the pediatric nasal mucosa at cellular resolution remains unresolved. Here, we generated a single-cell RNA sequencing atlas of 335,174 nasal epithelial and immune cells from 132 children under five years of age with SARS-CoV-2, rhinovirus, or respiratory syncytial virus (RSV) infection, alongside uninfected controls. Mapping viral transcripts to individual cells revealed virus-specific infected epithelial states: an NF-kB-responsive ciliated subset in SARS-CoV-2 and a previously undescribed KRT17+ squamous-like subset in RSV. We delineated divergent mucosal response programs, including a robust interferon (IFN) response in SARS-CoV-2, an IL-13-responsive secretory program in rhinovirus, and heightened inflammatory and cytotoxic immune activation in RSV. In RSV, specific immune subsets and elevated IFN-response signatures were associated with disease severity, whereas rhinovirus-induced wheeze was marked by expansion of a CST1+ goblet cell subset. Integration of asthma genome-wide association data with our atlas revealed a KRT13+ hillock-like squamous epithelial subset enriched for expression of childhood-onset asthma risk loci. Finally, we demonstrate that this resource enables high-resolution annotation of independent pediatric cohorts in Kolkata, India and rural Bangladesh. Together, this atlas establishes a comprehensive view of antiviral immunity in the pediatric nasal mucosa and defines virus-specific mucosal immune programs relevant to disease severity and asthma risk in early life.

immunology↗

bioRxiv2024

Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2

SARS-CoV-2 infection and COVID-19 disease vary with respect to viral variant and host vaccination status. However, how vaccines, emergent variants, and their intersection shift host responses in the human nasal mucosa remains uncharacterized. We and others have shown during the first SARS-CoV-2 wave that a muted nasal epithelial interferon response at the site of infection underlies severe COVID-19. We sought to further understand how upper airway cell subsets and states associate with COVID-19 phenotypes across viral variants and vaccination. Here, we integrated new single-cell RNA-sequencing (scRNA-seq) data from nasopharyngeal swabs collected from 67 adult participants during the Delta and Omicron waves with data from 45 participants collected during the original (Ancestral) wave in our prior study. By characterizing detailed cellular states during infection, we identified changes in epithelial and immune cells that are both unique and shared across variants and vaccination status. By defining SARS-CoV-2 RNA+ cells for each variant, we found that Delta samples had a marked increase in the abundance of viral RNA+ cells. Despite this dramatic increase in viral RNA+ cells in Delta cases, the nasal cellular compositions of Delta and Omicron exhibit greater similarity, driven partly by myeloid subsets, than the Ancestral landscapes associated with specialized epithelial subsets. We found that vaccination prior to infection was surprisingly associated with nasal macrophage recruitment and activation rather than adaptive immune cell signatures. While patients with severe disease caused by Ancestral or Delta variants had muted interferon responses, Omicron-infected patients had equivalent interferon responses regardless of disease severity. Our study defines the evolution of cellular targets and signatures of disease severity in the upper respiratory tract across SARS-CoV-2 variants, and suggests that intramuscular vaccines shape myeloid responses in the nasal mucosa upon SARS-CoV-2 infection.

immunology↗

bioRxiv2021

Protein allocation and utilization in the versatile chemolithoautotroph Cupriavidus necator

Bacteria must balance the different needs for substrate assimilation, growth functions, and resilience in order to thrive in their environment. Of all cellular macromolecules, the bacterial proteome is by far the most important resource and its size is limited. Here, we investigated how the highly versatile knallgas bacterium Cupriavidus necator reallocates protein resources when grown on different limiting substrates and with different growth rates. We determined protein quantity by mass spectrometry and estimated enzyme utilization by resource balance analysis modeling. We found that C. necator invests a large fraction of its proteome in functions that are hardly utilized. Of the enzymes that are utilized, many are present in excess abundance. One prominent example is the strong expression of CBB cycle genes such as Rubisco during growth on fructose. Modeling and mutant competition experiments suggest that CO2-reassimilation through Rubisco does not provide a fitness benefit for heterotrophic growth, but is rather an investment in readiness for autotrophy. HighlightsO_LIA large fraction of the C. necator proteome is not utilized and not essential C_LIO_LIHighly utilized enzymes are more abundant and less variable C_LIO_LIAutotrophy related enzymes are largely underutilized C_LIO_LIRe-assimilation of CO2 via the CBB cycle is unlikely to provide a fitness benefit C_LI

systems biology↗