Biology subjects

Laniewski, N.

Publications and source records attributed to Laniewski, N..

5 recordsLinked to original sources

bioRxiv2026

Single cell analysis of neonatal naïve CD8α+ T cells reveals novel subsets bridging the innate-adaptive spectrum

There is growing evidence that neonates harbor innate-like CD8a+ T cell subsets that contribute to both protection and hyper-inflammatory states. It remains unclear, however, where these innate-like features are found among the many conventional and unconventional T cell populations that can upregulate the CD8 receptor. Further delineation of these unique populations and functions, with a focus on CD8ab co-expression, will enable studies that seek to understand the unique immune features in conventional T cell populations that are present during fetal and early postnatal life. We used cord blood from infants across the full viable gestational age range to examine phenotypic and transcriptional heterogeneity, with a particular focus on the naive T cell pool. We report a set of fetally-derived and innate-like naive CD8{beta}+ T cells ( FITs) that are marked by their KLRG1+CD161+ phenotype, unique transcriptomic features and which are sparsely detected in adult peripheral blood. Additionally, using T cell receptor repertoire profiling, we can distinguish FITs from well-described and semi-invariant unconventional T cell populations such as mucosa-associated invariant T cells. Our delineation of FITs unique features will enable future investigation into their ontogeny and tissue distribution, and ultimately their role in immune-related outcomes in preterm infants.

immunology↗

bioRxiv2024

Gene Regulatory Programs that Specify Age-Related Differences during Thymocyte Development

T cell development is fundamental to immune system establishment, yet how this development changes with age remains poorly understood. Here, we construct a transcriptional and epigenetic atlas of T cell developmental programs in neonatal and adult mice, revealing the ontogeny of divergent gene regulatory programs and their link to age-related differences in phenotype and function. Specifically, we identify a gene module that diverges with age from the earliest stages of genesis and includes programs that govern effector response and cell cycle regulation. Moreover, we reveal that neonates possess more accessible chromatin during early thymocyte development, likely establishing poised gene expression programs that manifest later in thymocyte development. Finally, we leverage this atlas, employing a CRISPR-based perturbation approach coupled with single-cell RNA sequencing as a readout to uncover a conserved transcriptional regulator, Zbtb20, that contributes to age-dependent differences in T cell development. Altogether, our study defines transcriptional and epigenetic programs that regulate age-specific differences in T cell development.

genomics↗

bioRxiv2022

Fluximplied: A novel approach integrates rate limiting steps and differential expression for pathway analysis

BackgroundMany tools exist to perform a rigorous pathway analysis, though traditional gene set enrichment analysis remains among the most common. While useful for many applications, one common situation where it is less so is the metabolic profiling of bulk omics datasets. Rate limiting steps in more linear pathways are the main determinant of flux through these pathways, but differential expression of the enzymes that catalyze these steps is usually not differentially weighted in pathway analysis. Fluximplied was built to perform pathway analysis with rate limiting steps in mind to assess the implied flux through a number of well validated metabolic pathways. ResultsA database of rate limiting steps and their associated pathway was constructed. Using publicly available human RNA sequencing data from liver, putamen, and adipose tissue, fluximplied generally corroborated the pathway analysis. When comparing two CD8 T cell subsets from mouse lung, our algorithm confirmed previous findings that were not found previously. ConclusionFluximplied is an accessible tool for pathway analysis which is intended to assist the user with hypothesis generation. Unlike traditional approaches to pathway analysis, it specifically queries a database of rate limiting steps in order to infer flux through canonical metabolic pathways.

bioinformatics↗

bioRxiv2022

Lin28b specifies an innate-like lineage of CD8+ T cells in early life

The immune system is stratified into layers of specialized cells with distinct functions. Recently, Lin28b was shown to serve as a master regulator of fetal lymphopoiesis, programming the development of more innate-like lymphocytes in early life. However, it remains unclear whether Lin28b specifies innate functions in more conventional adaptive lymphocytes. In this report, we discovered that Lin28b promotes the development of a more innate-like lineage of CD8+ T cells that is capable of protecting the host against a wide variety of pathogens in the absence of TCR stimulation. Using RNA-seq and ATAC-seq, we found that Lin28b transcriptionally and epigenetically programs CD8+ T cells to be highly responsive to innate cytokines. We also performed scRNAseq and found that the shift from innate-like CD8+ T cells in early life to adaptive CD8+ T cells in adulthood is mediated by changes in the abundance of distinct subsets of cells. Remarkably, the innate CD8+ T cell subset predominates in early life but is also present in adult mice and humans. Collectively, our findings demonstrate that neonatal CD8+ T cells are a distinct lineage of lymphocytes that provide the host with innate defense in early life. One sentence SummaryHigh-dimensional analysis reveals how Lin28b programs neonatal CD8+ T cells for innate defense.

immunology↗

bioRxiv2019

Coordinated Postnatal Trajectories of T Cells and Microbiota in Preterm and Full- term Newborns

Neonatal immune-microbiota co-development is poorly understood, yet appropriate recognition of - and response to - pathogens and commensal microbiota is critical to health. In this longitudinal study of 148 pre- and 119 full-term infants from birth through one year of age we found that postmenstrual age, or weeks from conception, not post-natal age, is the dominant factor influencing T cell and mucosal microbiota development. Numerous features of the T cell and microbiota functional development remain unexplained, however, by either age metric and are instead shaped by discrete peri- and post-natal events. Most strikingly, we establish that prenatal antibiotics or infection disrupt the normal T cell population developmental trajectory, influencing subsequent respiratory microbial colonization and predicting respiratory morbidity. In this way, early exposures imprint the postnatal immune-microbiota axis and place an infant at significant risk for respiratory morbidity in early childhood. One Sentence SummaryT cells and microbiota follow predictable, coordinated trajectories in newborns, and their coordination is an important determinant of illness in the first year. Graphical AbstractNasal and rectal microbiome was assessed weekly in the NICU, monthly post-discharge, and when respiratory illness symptoms occurred. T cells were characterized at birth (cord blood), 36-42 weeks postmenstrual age, and at 12 months. Quarterly respiratory morbidity surveys determined the 12-month outcome of persistent respiratory disease. More frequent illnesses and chronic disease outcomes occurred by one year of age if development of these systems was discordant or disrupted. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/736090v3_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1f08adeorg.highwire.dtl.DTLVardef@12d3671org.highwire.dtl.DTLVardef@151396borg.highwire.dtl.DTLVardef@190dcff_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗