Biology subjects

Joshi, N. V.

Publications and source records attributed to Joshi, N. V..

4 recordsLinked to original sources

bioRxiv2023

High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester

BackgroundThe placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal- fetal health. MethodsThe normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. ResultsPlacenta expresses 14,979 mRNAs above sequencing noise (TPM>0.66), with 1,545 stably expressed genes across gestation. Differentially expressed genes account for 86.7% of genes in the full cohort (FDR<0.05). Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR<0.001, fold change>1.5), there are 6,941 differentially expressed protein coding genes (3,206 upregulated in first and 3,735 upregulated in third trimester). ConclusionThis is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and stably expressed genes may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers in maternal-fetal disease.

developmental biology↗

bioRxiv2021

Sex differences in microRNA expression in first and third trimester human placenta

Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be the result of sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing was used to identify miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n=113) and parturition (n=47). Sequencing and differential expression (DE) analysis identified 432 mature miRNAs expressed in the first trimester female, 425 in the first trimester male, 400 in the third trimester female, and 508 in the third trimester male placenta (baseMean >10). Of these, 11 sexually dimorphic (FDR<0.05, baseMean >10) miRNAs were identified in the first and 4 miRNAs were identified in the third trimester, including miR-361-5p, significant in both trimesters, all upregulated in females. Across gestation, 207 miRNAs were DE across gestation, common to both females and males, miR-4483, the most DE across gestation. There were twice as many female-specific differences across gestation as male-specific (44 miRNAs vs 21 miRNAs), indicating that miRNA abundance across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex independent and sex specific placenta miRNA atlas across gestation which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences. Summary SentenceSex dimorphism in miRNA expression is more pronounced in first compared to third trimester placenta, and there are twice as many female-specific gestational differences, indicating miRNA abundance across human gestation is also sexually dimorphic.

developmental biology↗

bioRxiv2021

High-throughput miRNA-sequencing of the human placenta: expression throughout gestation

BackgroundAltered placenta miRNA abundance may impact the maternal-fetal interface and pregnancy outcomes. Understanding miRNA changes across gestation is essential before miRNAs can be used as biomarkers or prognostic indicators during pregnancy. Materials & MethodsUsing next-generation sequencing, we characterize the normative human placenta miRNA transcriptome in first (N=113) and third trimester (N=47). ResultsThere are 801 miRNAs expressed in both first and third trimester, including 182 with similar expression across gestation (P[≥]0.05) and 182 significantly different (FDR<0.05). Of placenta-specific miRNA clusters, C14MC is more upregulated in first trimester and C19MC is more highly expressed overall. ConclusionThis work provides a rich atlas of healthy pregnancies to direct functional studies investigating the epigenetic differences in first and third trimester placentae. Lay AbstractThe human body produces microRNAs which affect the expression of genes and proteins. This study uses next generation sequencing to identify the microRNA profile of first and third trimester human placentae using a large cohort (N=113 first, N=47 third trimester). All pregnancies resulted in healthy babies. We identify microRNAs with significantly different expression between first and third trimester, as well as stably expressed microRNAs. This work provides a baseline for future studies which may use microRNAs to monitor maternal-fetal health throughout pregnancy.

developmental biology↗

bioRxiv2019

The pericardium promotes cardiac repair and remodelling post-myocardial infarction

The pericardium is widely recognised for its lubricating and bio-mechanical properties. It also contains fat-associated lymphoid clusters (FALCs) and its immune functions have been widely overlooked. Here we aimed to assess the inflammatory activity of the pericardium in patients who suffered a recent myocardial infarction (MI) and to determine its importance for repair and remodelling in a murine MI model induced by coronary artery ligation (CAL). By comparing 18F-fluorodeoxyglucose (FDG) activity in the pericardium of patients with stable coronary artery disease and patients who had a recent MI, we demonstrate that MI is associated with increased pericardial inflammation. We confirm in mice, that pericardial FALCs undergo a major expansion following CAL. We show that despite similar initial injury, removal of the pericardium prior to MI disrupted subsequent repair, resulting in 50% mortality due to cardiac rupture, while all mice with intact pericardia survived. Removal of the pericardium also led to decreased staining for Ym1, a marker of reparative macrophages and adverse cardiac fibrosis within the infarct area. Together, this work indicates a crucial role for the pericardium in regulating inflammation, macrophage polarisation and tissue remodelling in the heart following MI.

physiology↗