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Fetal maturation revealed by amniotic fluid cell-free transcriptome in rhesus macaques
Augusto F. Schmidt, Daniel J. Schnell, Kenneth P. Eaton, Kashish Chetal, Paranthaman S. Kannan, Lisa A. Miller, Claire A. Chougnet, Daniel T. Swarr, Alan H. Jobe, Nathan Salomonis, Beena D. Kamath-Rayne
Augusto F. Schmidt, Daniel J. Schnell, Kenneth P. Eaton, Kashish Chetal, Paranthaman S. Kannan, Lisa A. Miller, Claire A. Chougnet, Daniel T. Swarr, Alan H. Jobe, Nathan Salomonis, Beena D. Kamath-Rayne
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Research Article Reproductive biology

Fetal maturation revealed by amniotic fluid cell-free transcriptome in rhesus macaques

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Abstract

Accurate estimate of fetal maturity could provide individualized guidance for delivery of complicated pregnancies. However, current methods are invasive, have low accuracy, and are limited to fetal lung maturation. To identify diagnostic gestational biomarkers, we performed transcriptomic profiling of lung and brain, as well as cell-free RNA from amniotic fluid of preterm and term rhesus macaque fetuses. These data identify potentially new and prior-associated gestational age differences in distinct lung and neuronal cell populations when compared with existing single-cell and bulk RNA-Seq data. Comparative analyses found hundreds of genes coincidently induced in lung and amniotic fluid, along with dozens in brain and amniotic fluid. These data enable creation of computational models that accurately predict lung compliance from amniotic fluid and lung transcriptome of preterm fetuses treated with antenatal corticosteroids. Importantly, antenatal steroids induced off-target gene expression changes in the brain, impinging upon synaptic transmission and neuronal and glial maturation, as this could have long-term consequences on brain development. Cell-free RNA in amniotic fluid may provide a substrate of global fetal maturation markers for personalized management of at-risk pregnancies.

Authors

Augusto F. Schmidt, Daniel J. Schnell, Kenneth P. Eaton, Kashish Chetal, Paranthaman S. Kannan, Lisa A. Miller, Claire A. Chougnet, Daniel T. Swarr, Alan H. Jobe, Nathan Salomonis, Beena D. Kamath-Rayne

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Figure 3

Detection of tissue maturation programs in amniotic fluid.

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Detection of tissue maturation programs in amniotic fluid.
(A and C) Vol...
(A and C) Volcano plot of gene expression correlation (Spearman’s rank, controlling for treatment year) from the same animals (treatment and controls) in (A) amniotic fluid and lungs or (C) amniotic fluid and hippocampus. Spearman P value and rank correlation are shown in the plot, with genes previously observed to be induced in human amniotic fluid, called out and designated by red (significant correlation) or blue (nonsignificant) in A. In C, the top significant genes (Spearman’s correlation ≥ 0.5 and P < 0.003) are designated in blue. Triangle markers denote FDR-adjusted P < 0.05. (B and D) Gene-set enrichment of all available single-cell, cell type signatures for (B) amniotic-fluid/lung positively correlated transcripts (P ≤ 0.05) or (D) amniotic-fluid/brain positively correlated transcripts. Gene sets for lung associated with lung are specifically denoted in B, and those for muscle, brain, or endothelial (most frequently enriched) are denoted in D. n = 35 paired samples for lung with amniotic fluid and hippocampus with amniotic fluid.

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