Biology subjects

Manuel, G.

Publications and source records attributed to Manuel, G..

5 recordsLinked to original sources

bioRxiv2026

A single-cell transcriptomic atlas of the periventricular proliferative zone in the late gestation fetal brain in the pigtail macaque

BackgroundThe fetal brain undergoes rapid changes in late gestation, when waves of neurogenesis and gliogenesis shape cortical circuitry. The periventricular proliferative region and adjacent white matter are enriched in neuroprogenitor cells, newborn neurons, and interneurons, which is challenging to study in the late gestation human fetal brain. The nonhuman primate (NHP) provides a powerful translational model to overcome this limitation, given its close similarity to human neurodevelopmental trajectories. The study objective was to construct a single-cell RNA-Seq (scRNA-Seq) atlas of the late-gestation fetal brain of the pigtail macaque (Macaca nemestrina), focused on the periventricular proliferative zone. MethodsA sample of the lateral ventricular wall, subventricular zone, and overlying white/gray matter was dissociated into single cells and processed through the 10X Genomics pipeline, followed by SoupX removal of ambient RNA, and Seurats pipeline to aggregate, cluster and annotate single-cell populations. Monocle3 was used to determine pseudotime and map lineage progression. ResultsThis analysis captured diverse populations of neuroprogenitors, newborn neurons, developing lineages of excitatory and inhibitory neurons, oligodendrocyte and astrocyte lineages, and resident immune and endothelial cells. ConclusionsSingle-cell populations from the third-trimester nonhuman primate fetal brain are highly similar to those in the human fetus. This late-gestation single-cell atlas of the periventricular proliferative zone provides a unique reference for progenitor, neuronal, glial, vascular, and immune cell states during a critical window of primate neurodevelopment, enabling mechanistic interrogation of how inflammatory, infectious, or hypoxic insults disrupt vulnerable neurogenic niches.

genomics↗

bioRxiv2025

Maternal Influenza A Virus Infection Induces Antiviral and Immune Dysregulation in the Placenta and Fetus Without Vertical Transmission

Influenza A virus (IAV) infection during pregnancy is associated with stillbirth and preterm birth, but the degree to which IAV alters placental and fetal immunity is poorly understood. The objective of our study was to determine the immunologic impact of maternal IAV infection on the placenta and fetus in a pigtail macaque (Macaca nemestrina) model. Pregnant pigtail macaques were inoculated with 107 plaque forming units (PFU) of IAV [A/California/07/2009 (H1N1)] and underwent necropsy 5 days post-infection (N=11). Results were compared to uninfected historical controls (N=16). IAV inoculation induced maternal pneumonia in all cases. Stillbirth occurred in 18% (2/11) of IAV-infected pregnancies, but not in controls. While vertical transmission was not observed, low-level IAV viral RNA was detected in two placentas. In the placenta, maternal IAV infection was associated with increased IL-1{beta}, IL-18, and IFN-{beta} levels, and an upregulated type I interferon (IFN) transcriptional response. IAV infection was also associated with significantly higher frequencies of intermediate and non-classical monocytes, plasmacytoid dendritic cells, CD4 T cells, and NKT cells in the fetus (lung, lymph node, blood). Although placental immune and transcriptional perturbations were rarely correlated with maternal IAV disease indicators (e.g., maternal lung viral load/IFN-/IFN-{beta}/IL-6), there were consistent and significant correlations between these metrics and perturbed immune cell populations in the fetus (CD4+ and CD8+ T cells, plasmacytoid dendritic cells, monocyte sub-populations). Maternal IAV infection disrupted both placental and fetal immune environments, but only fetal immune alterations correlated with maternal lung disease severity. One Sentence SummaryMaternal influenza A virus infection in pregnant pigtail macaques dysregulates placental and fetal immunity, with disease severity correlating strongly with fetal, but not placental, immune perturbations.

systems biology↗

bioRxiv2025

A single-cell transcriptomic atlas of the pigtail macaque placenta in late gestation

The placenta is a complex organ with multiple immune and non-immune cell types that promote fetal tolerance and facilitate the transfer of nutrients and oxygen. The nonhuman primate (NHP) is a key experimental model for studying human pregnancy complications, in part due to similarities in placental structure, which makes it essential to understand how single-cell populations compare across the human and NHP maternal-fetal interface. We constructed a single-cell RNA-Seq (scRNA-Seq) atlas of the placenta from the pigtail macaque (Macaca nemestrina) in the third trimester, comprising three different tissues at the maternal-fetal interface: the chorionic villi (placental disc), chorioamniotic membranes, and the maternal decidua. Each tissue was separately dissociated into single cells and processed through the 10X Genomics and Seurat pipeline, followed by aggregation, unsupervised clustering, and cluster annotation. Next, we determined the maternal-fetal origins of cell populations and analyzed single-cell RNA trajectory, Gene Ontology enrichment, and cell-cell communication. Single-cell populations in the pigtail macaque were strikingly similar in their identity and frequency to those found in the human placenta, including cells from trophoblast, stromal cell, immune, and macrophage lineages. An advantage of our approach was the deep sequencing of three tissues at the maternal-fetal interface, which yielded a rich diversity of common and rare single-cell populations. The third-trimester pigtail macaque single-cell atlas enables the identification of cellular subclusters analogous to those in humans and provides a powerful resource for understanding experimental perturbations on the NHP placenta.

genomics↗

bioRxiv2024

Engineering a ribozyme with aminoacyl-tRNA synthetase activity

A ribozyme that can charge a tRNA with amino acids and discriminate between cognate and non-cognate tRNAs is of interest because an RNA with this ability may have been a critical for translation in the transition from the RNA world. In addition, it could provide a tool for incorporating non-canonical amino acids for biotechnology applications. Here, we rationally engineer a ribozyme by fusing a tRNA binding module derived from a T-box riboswitch with a catalytic module (a flexizyme) to generate a ribozyme that can amino acylate a target tRNA. We demonstrate that this ribozyme be readily redesigned to alter tRNA specificity. This ribozyme is compatible with an in vitro translation system and could be used to recode a protein sequence to site-specifically incorporate a non-canonical amino acid.

biochemistry↗

bioRxiv2024

Serological screening in animals combined with environmental surveys provides definite proof of the local establishment of Burkholderia pseudomallei in Guadeloupe

BackgroundMelioidosis is an emerging infectious disease caused by the soil-dwelling bacterium Burkholderia pseudomallei that affects both humans and animals. It is endemic in South and Southeast Asia, and northern Australia, causing an estimated 165,000 human cases annually worldwide. Human cases have been reported in the French West Indies (Martinique and Guadeloupe) since the 1990s. Conversely, no human cases have been reported in French Guiana, a French territory in South America. Our study aimed to investigate whether B. pseudomallei is locally established in Guadeloupe and French Guiana. We assessed animal exposure by serology and examined the presence of B. pseudomallei in the environment of seropositive animals. Methodology/Principal findingsBlood samples were collected from domestic animals in two goat farms in Les Saintes, Guadeloupe (n=31), and in 56 farms in French Guiana (n=670) and tested by ELISA. Serological follow up was performed on selected farms. Soil, water and goat rectal swabs were collected and analysed by culture and PCR. In French Guiana, the highest prevalence rates were observed in equids (24%) and cattle (16%), while in Les Saintes, a prevalence of 39% was observed in goats. The longitudinal study in Les Saintes revealed consistent high seropositivity in goats. A B. pseudomallei strain was isolated from the soil from one of the farms and detected in goat rectal swabs from the other farm. Conclusions/SignificanceOur environmental investigation prompted by the serologic data confirms the presence of B. pseudomallei in Les Saintes, consistent with documented human cases of melioidosis on this island. In French Guiana, our serologic results call for environmental surveys and a re-evaluation of human infections with melioidosis-like symptoms. The approach developed in this study may help to identify high-risk areas that warrant further investigation. Author summaryBurkholderia pseudomallei, an environmental bacterium, is the causative agent of melioidosis in humans and animals. If the disease has been historically reported to be endemic in South Asia and northern Australia, recent studies reveal its presence outside of these territories, both in the environment and among patients who have not travelled to endemic areas. Furthermore, the projected increase in extreme climatic events in the near future could increase the prevalence of the disease as well as cause its emergence in new territories. For these reasons, it is important to identify new areas at risk. Our study aimed to investigate the presence of the pathogen in French West Indies. We combined surveys in domestic animals (cattle, goats, horses, sheep, and pigs) and in the environment. The identification of seropositive animals without clinical signs, together with the isolation of B. pseudomallei in the environment of a goat farm in Guadeloupe, underscores the importance of including melioidosis in animal surveillance programs. The use of serologic methods can help identify animal exposure to the pathogen, thereby helping to identify areas where the pathogen may be present in the environment.

microbiology↗