Role of sex as a biological variable in neonatal alveolar macrophages
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ABSTRACT:
PROVIDER: PRJNA1111874 | ENA |
REPOSITORIES: ENA
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Project description:Recovery from lung injury during the neonatal period requires the orchestration of many biological pathways. Modulation of biological pathways can drive the developing lung towards proper repair or persistent maldevelopment after injury that can lead to a disease phenotype. Sex as a biological variable can modulate these pathways differently in the male and female lung exposed to neonatal hyperoxia. In this study, we assessed the contribution of cellular diversity in the male and female neonatal lung following injury. Our objective was to investigate sex and cell-type specific transcriptional changes that drive repair or persistent injury in the neonatal lung at single-cell resolution and delineate the alterations in the immune-endothelial cell communication networks in the developing lung using single cell RNA sequencing (sc-RNAseq) in a murine model of hyperoxic lung injury. We generated transcriptional profiles of >55,000 cells isolated from the lungs of postnatal day 1 (PND 1) andpostnatal day 21 (PND 21) neonatal male and female C57BL/6 mice exposed to 95% FiO2between PND 1-5 (saccular stage of lung development).We show the presence of sex-based differences in the transcriptional states of lung endothelial and immune cells at PND 1 and PND 21. Furthermore, we demonstrate that biological sex significantly influences the response to injury, with a greater number of differentially expressed genes showing sex-specific patterns than those shared between male and female lungs. Pseudotime trajectory analysis highlighted genes needed for lung development that were altered by hyperoxia. Finally, we show intercellular communication between endothelial and immune cells at saccular and alveolar stages of lung development with sex-based biases in the cross-talk and identify novel ligand-receptor pairs. Our findings provide valuable insights into the cell diversity, transcriptional state, developmental trajectory, and cell-cell communication underlying neonatal lung injury, with implications for understanding lung development and therapeutic interventions while highlighting the crucial role of sex as a biological variable.
2023-11-15 | GSE237944 | GEO
Project description:In this study, lung alveolar macrophages were sorted and subjected to bulk RNA-Seq from male and female neonatal lungs.
2024-08-05 | GSE267573 | GEO
Project description:Bronchopulmonary dysplasia (BPD) is characterized by an arrest in alveolarization, abnormal vascular development and variable interstitial fibroproliferation in the premature lung. Endothelial to mesenchymal transition (Endo-MT) may be a source of pathologic fibrosis in many organ systems. Whether Endo-MT contributes to the pathogenesis of BPD is not known. We tested the hypothesis that pulmonary endothelial cells will show increased expression of Endo-MT markers upon exposure to hyperoxia and that sex as a biological variable will modulate differences in expression. WT and Cdh5-PAC CreERT2 (endothelial reporter) neonatal male and female mice (C57BL6) were exposed to hyperoxia (0.95 FiO2) either during the saccular stage of lung development (95% FiO2; PND1-5) or through the saccular and early alveolar stages of lung development (75% FiO2; PND1-14). Expression of Endo-MT markers were measured in whole lung and endothelial cell mRNA. Sorted lung endothelial cells were subjected to bulk RNA-Seq. We show that exposure of the neonatal lung to hyperoxia leads to upregulation of key markers of EndoMT Neonatal male mice show higher expression of genes related to EndoMT. Furthermore, using lung sc-RNAseq data from neonatal lung we were able to show that xxx. Markers related to Endo-MT are upregulated in the neonatal lung upon exposure to hyperoxia and show sex-specific differences. Mechanisms mediating EndoMT in the injured neonatal lung can modulate the response of the neonatal lung to hyperoxic injury and need further investigation.
2023-11-08 | GSE230672 | GEO
Project description:Modulation of Recovery from Neonatal Hyperoxic Lung Injury by Sex as a Biological Variable
| PRJNA997284 | ENA
Project description:Endothelial to Mesenchymal Transition in Neonatal Hyperoxic Lung Injury: Role of sex as a biological variable
| PRJNA962106 | ENA
Project description:The goal of the project was to delineate sex-specific differences in the neonatal lung exposed to postnatal hyperoxia to model the pathophysiologic mechanisms in the human disease; bronchopulmonary dysplasia (BPD).
2022-10-25 | GSE211356 | GEO
Project description:Remarkable Lung Heterogeneity at Single-Cell Resolution and the Role of Sex as a Biological Variable in Neonatal Hyperoxic Lung Injury
| PRJNA869954 | ENA
Project description:The tips of secondary alveolar septae in day 6 neonatal mouse lung tissue were isolated using laser capture microscopy. RNA was isolated from pooled secondary alveolar tips and also from pooled neonatal day 6 whole lung tissue. The isolated RNAs were then amplified in parallel. Gene array profiling of the two RNA samples was performed. Gene expression in the secondary alveolar septal tips was compared to gene expression in the whole lung tissue. In this way, the genes that are expressed in the tip of secondary alveolar septae were identified as well as the genes that are enriched in the alveolar septal tips versus in whole lung tissue. Experiment Overall Design: We performed an experiment in which we used laser capture microscopy to collect 10,000 secondary alveolar tips from frozen sections of lung tissue obtained from many different day 6 neonatal mice obtained from different litters. In the same experiment, we also isolated RNA from pooled day 6 neonate whole lung tissue. The isolated RNAs were amplified in parallel and then hybridized to microarrays in parallel in order to profile and compare gene expression in the two samples. The entire experiment was performed twice with tissue from different litters. In addition, the amplified RNAs were hybridized to two different microarrays, at different times.
2008-06-12 | E-GEOD-4220 | biostudies-arrayexpress
Project description:The tips of secondary alveolar septae in day 6 neonatal mouse lung tissue were isolated using laser capture microscopy. RNA was isolated from pooled secondary alveolar tips and also from pooled neonatal day 6 whole lung tissue. The isolated RNAs were then amplified in parallel. Gene array profiling of the two RNA samples was performed. Gene expression in the secondary alveolar septal tips was compared to gene expression in the whole lung tissue. In this way, the genes that are expressed in the tip of secondary alveolar septae were identified as well as the genes that are enriched in the alveolar septal tips versus in whole lung tissue. Keywords: Comparison of gene profiles in the tips of secondary alveolar septae versus in whole lung tissue of neonatal mice
2006-08-19 | GSE4220 | GEO
Project description:Phlebotomy-induced anemia (PIA) is universal and highly variable in degree among preterm infants. PIA contributes to the preterm infant’s considerable neurodevelopmental risk. In the mouse, neonatal PIA causes brain tissue hypoxia and iron deficiency accompanied by long-term sex-dependent neurobehavioral abnormalities. The neuroregulatory pathways disrupted by PIA underlying these effects are unknown. This study determined the effects of PIA severity and sex on the hippocampal transcriptome of young mice. ). NGS data from mPIA females showed the least DEGs (0.5% of >22,000 genes) whereas sPIA females had the most (8.6%), indicating a dose-dependent effect. Conversely, mPIA and sPIA males showed similar changes in gene expression (5.3% and 4.7%, respectively), indicating a threshold effect. DEGs were further analyzed using the knowledge-based Ingenuity Pathway Analysis (IPA) to determine altered functional and gene networks. The patterns of gene changes induced by PIA indicate sex-specific and dose-dependent effects with increased pro-inflammation in females and decreased neurodevelopment in males. These changes may underlie the documented reduced recognition memory function in male and abnormal social-cognitive behavior in female adult mice following neonatal PIA. Collectively, these results parallel clinical studies demonstrating sex-specific behavioral outcomes as a function of neonatal anemia management.
2021-07-13 | GSE179877 | GEO