Biology subjects

Arenas-Hernandez, M.

Publications and source records attributed to Arenas-Hernandez, M..

4 recordsLinked to original sources

bioRxiv2025

Single-Cell Comparison of Schwann and Fibroblast Cells Reveals Distinct Transcriptional Programs in NF1-Associated Neurofibromas

Neurofibromatosis type 1 (NF1) is an inherited tumor predisposition syndrome characterized by the development of benign peripheral nerve sheath tumors, most commonly cutaneous neurofibromas (cNFs) and plexiform neurofibromas (pNFs). Although both tumor types arise from Schwann cells and share NF1 loss as a genetic driver, they differ markedly in growth behavior, microenvironmental context, and clinical outcomes, with pNFs carrying risk of malignant transformation. To define transcriptional programs that underlie these differences, we performed an integrative single-cell RNA sequencing analysis of Schwann cells and fibroblasts from cNF and pNF tumors, alongside NF1-expressing reference populations derived from human skin and nerve. This approach enabled us to disentangle NF1-dependent transcriptional changes from tissue-of-origin effects. We identified distinct Schwann cell states that separated tumor from non-tumor populations and further distinguished cNFs from pNFs, highlighting both shared disease-associated features and subtype-specific adaptations. These findings establish a framework for understanding how NF1 loss interacts with developmental origin and tissue context to shape divergent tumor phenotypes and may inform strategies for therapeutic targeting in NF1-associated neurofibromas.

cancer biology↗

bioRxiv2023

MNRR1 activation by nitazoxanide abrogates lipopolysaccharide- induced preterm birth in mice

Intra-amniotic inflammation leading to preterm birth is one of the leading causes of neonatal morbidity and mortality. We recently found that the mitochondrial levels of MNRR1 (Mitochondrial Nuclear Retrograde, Regulator 1; also called CHCHD2, AAG10, or PARK22), an important bi-organellar regulator of cellular function, are reduced in the context of inflammation and that both genetic and pharmacological increase in MNRR1 levels can counter the inflammatory profile. We show here that nitazoxanide, a clinically-approved drug, is an activator of MNRR1 and prevents preterm birth in a well-characterized murine model caused by intra-amniotic lipopolysaccharide (LPS) injection. HighlightsO_LINitazoxanide exerts anti-inflammatory functions via activation of MNRR1. C_LIO_LIOral administration of nitazoxanide prevents preterm birth in mouse model of intra-intraamniotic LPS-induced inflammation. C_LI

immunology↗

bioRxiv2022

Microbiota of the pregnant mouse: characterization of the bacterial communities in the oral cavity, lung, intestine, and vagina through culture and DNA sequencing

Mice are frequently used as animal models for mechanistic studies of infection and obstetrical disease, yet characterization of the murine microbiota during pregnancy is lacking. The objective of this study was to therefore characterize the microbiotas of distinct body sites of the pregnant mouse that harbor microorganisms that could potentially invade the murine amniotic cavity leading to adverse pregnancy outcomes: vagina, oral cavity, intestine, and lung. The microbiotas of these body sites were characterized through anoxic, hypoxic, and oxic culture, as well as through 16S rRNA gene sequencing. With the exception of the vagina, the cultured microbiotas of each body site varied with atmosphere, with the greatest diversity in the cultured microbiota appearing under anoxic conditions. Only cultures of the vagina were able to recapitulate the microbiota observed from direct DNA sequencing of body site samples, primarily due to the dominance of two Rodentibacter strains. Identified as R. pneumotropicus and R. heylii, these isolates exhibited dominance patterns similar to those of Lactobacillus crispatus and L. iners in the human vagina. Whole genome sequencing of these Rodentibacter strains revealed shared genomic features, including the ability to degrade glycogen, an abundant polysaccharide in the vagina. In summary, we report body site specific microbiotas in the pregnant mouse with potential ecological parallels to those of humans. Importantly, our findings indicate that the vaginal microbiota of pregnant mice can be readily cultured, suggesting that mock vaginal microbiotas can be tractably generated and maintained for experimental manipulation in future mechanistic studies of host vaginal-microbiome interactions. IMPORTANCEMice are widely utilized as animal models of obstetrical complications; however, the characterization of the murine microbiota has been neglected during pregnancy. Microorganisms from the vagina, oral cavity, intestine, and lung have been found in the intra-amniotic space, where their presence threatens the progression of gestation. Herein, we characterize the microbiotas of pregnant mice and establish the appropriateness of culture in capturing the microbiota at each site. The high relative abundance of Rodentibacter observed in the vagina is similar to that of Lactobacillus in humans, suggesting potential ecological parallels. Importantly, we report that the vaginal microbiota of the pregnant mouse can be readily cultured under hypoxic conditions, demonstrating that mock microbial communities can be utilized to test the potential ecological parallels between microbiotas in human and murine pregnancy, and to evaluate the relevance of the structure of these microbiotas for adverse pregnancy outcomes, especially intra-amniotic infection and spontaneous preterm birth.

microbiology↗

bioRxiv2019

No consistent evidence for microbiota in murine placental and fetal tissues

The existence of a placental microbiota and in utero colonization of the fetus has been the subject of recent debate. The objective of this study was to determine whether the placental and fetal tissues of mice harbor bacterial communities. Bacterial profiles of the placenta and fetal brain, lung, liver, and intestine were characterized through culture, qPCR, and 16S rRNA gene sequencing. These profiles were compared to those of the maternal mouth, lung, liver, uterus, cervix, vagina, and intestine, as well as to background technical controls. Positive bacterial cultures from placental and fetal tissues were rare; of the 165 total bacterial cultures of placental tissues from the 11 mice included in this study, only nine yielded at least a single colony, and five of those nine positive cultures came from a single mouse. Cultures of fetal intestinal tissues yielded just a single bacterial isolate: Staphylococcus hominis, a common skin bacterium. Bacterial loads of placental and fetal brain, lung, liver, and intestinal tissues were not higher than those of DNA contamination controls and did not yield substantive 16S rRNA gene sequencing libraries. From all placental or fetal tissues (N = 49), there was only a single bacterial isolate that came from a fetal brain sample having a bacterial load higher than that of contamination controls and that was identified in sequence-based surveys of at least one of its corresponding maternal samples. Therefore, using multiple modes of microbiologic inquiry, there was not consistent evidence of bacterial communities in the placental and fetal tissues of mice. IMPORTANCEThe prevailing paradigm in obstetrics has been the sterile womb hypothesis, which posits that fetuses are first colonized by microorganisms during the delivery process. However, some are now suggesting that fetuses are consistently colonized by microorganisms in utero by microbial communities that inhabit the placenta and intra-amniotic environment. Given the established causal role of microbial invasion of the amniotic cavity (i.e. intra-amniotic infection) in pregnancy complications, especially preterm birth, if the in utero colonization hypothesis were true, there are several aspects of current understanding that will need to be reconsidered including the magnitude of intra-amniotic microbial load required to cause disease and their potential influence on the ontogeny of the immune system. However, acceptance of the in utero colonization hypothesis is premature. Herein, we do not find consistent evidence for placental and fetal microbiota in mice using culture, qPCR, and DNA sequencing.

microbiology↗