Distinct hepatocyte adaptations during gestation and lactation [pregnant_liver_mm10]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE294857 | GEO | 2025/09/02
REPOSITORIES: GEO
Similar Datasets
Project description:Using high-resolution single-cell RNA sequencing, we systematically characterized hepatocyte adaptations in mice across pregnancy and postpartum stages. We discovered a cyclical hepatocyte trajectory (“pregnancy clock”) governing metabolic changes during gestation and postpartum recovery, which reverted to pregestational states in non-lactating mice. Lactation induced a distinct branching trajectory characterized by elevated lipid synthesis and export. Deletion of gp130 disrupted hepatic adaptations during pregnancy, impairing fetal growth, whereas ACSS2 deficiency postpartum disrupted lipid export, affecting milk quality and offspring growth.
2025-09-02 | GSE294860 | GEO
Project description:Using high-resolution single-cell RNA sequencing, we systematically characterized hepatocyte adaptations in mice across pregnancy and postpartum stages. We discovered a cyclical hepatocyte trajectory (“pregnancy clock”) governing metabolic changes during gestation and postpartum recovery, which reverted to pregestational states in non-lactating mice. Lactation induced a distinct branching trajectory characterized by elevated lipid synthesis and export. Deletion of gp130 disrupted hepatic adaptations during pregnancy, impairing fetal growth, whereas ACSS2 deficiency postpartum disrupted lipid export, affecting milk quality and offspring growth.
2025-09-02 | GSE294859 | GEO
Project description:The liver undergoes adaptive changes during pregnancy and lactation to meet specific physiological demands, but the precise processes, regulatory mechanisms, and functions remain unclear. Using high-resolution single-cell RNA sequencing (scRNA-seq), we comprehensively analyzed hepatocyte adaptations in mice throughout these periods. Our findings revealed a circular trajectory, termed the “pregnancy clock”, during gestation and non-lactating postpartum phases, reverting to the pre-gestation state after recovery. In contrast, lactation induced a distinct branching pathway, characterized by increased fatty acid synthesis and lipid accumulation. Deletion of Gp130 in the JAK/STAT pathway disrupted gestation transitions, leading to delayed embryonic development, while ACSS2 ablation impaired postpartum lipid metabolism, affecting milk quality and offspring growth. Comparative analysis with sheep demonstrated conserved hepatocyte adaptation pathways despite species-specific genetic regulatory networks. These insights offer potential targets for therapeutic interventions to optimize maternal and fetal health and enhance lactation efficiency, with broad implications for reproductive biology and livestock management.
2025-09-02 | GSE272943 | GEO
Project description:The liver undergoes adaptive changes during pregnancy and lactation to meet specific physiological demands, but the precise processes, regulatory mechanisms, and functions remain unclear. Using high-resolution single-cell RNA sequencing (scRNA-seq), we comprehensively analyzed hepatocyte adaptations in mice throughout these periods. Our findings revealed a circular trajectory, termed the “pregnancy clock”, during gestation and non-lactating postpartum phases, reverting to the pre-gestation state after recovery. In contrast, lactation induced a distinct branching pathway, characterized by increased fatty acid synthesis and lipid accumulation. Deletion of Gp130 in the JAK/STAT pathway disrupted gestation transitions, leading to delayed embryonic development, while ACSS2 ablation impaired postpartum lipid metabolism, affecting milk quality and offspring growth. Comparative analysis with sheep demonstrated conserved hepatocyte adaptation pathways despite species-specific genetic regulatory networks. These insights offer potential targets for therapeutic interventions to optimize maternal and fetal health and enhance lactation efficiency, with broad implications for reproductive biology and livestock management.
2025-09-02 | GSE272944 | GEO
Project description:Pancreatic β-cell mass expands during pregnancy and regresses in the postpartum period in conjunction with dynamic metabolic demands on maternal glucose homeostasis. To understand transcriptional changes driving these adaptations in β-cells and other islet cell types, we performed single-cell RNA sequencing on islets from virgin, late gestation, and early postpartum mice. We identified transcriptional signatures unique to gestation and the postpartum in β-cells, including induction of the AP-1 transcription factor subunits and other genes involved in the immediate-early response (IEGs). Additionally, we found pregnancy and postpartum-induced changes differed within each endocrine cell type, and in endothelial cells and macrophages within islets. Together, our data reveal novel insights into cell-type specific transcriptional changes responsible for adaptations by islet cells to pregnancy and their resolution postpartum.
2023-03-07 | GSE226788 | GEO
Project description:Biomolecules preserved in dental pulp are increasingly being used to identify individuals in the context of forensics and archaeology. Despite the vast amount of research into host and pathogen DNA, the potential use of physiologically informative proteins preserved in dental pulp has rarely been studied. Here, we hypothesized that pregnancy specific proteins circulating in the blood could be identified from the dental pulp of postpartum individuals and this was investigated using 8 human third molars extracted from 4 postpartum and 3 control individuals during clinical treatment. A total of 885 proteins were identified from these 8 dental pulp samples using liquid chromatography coupled tandem mass spectrometry, whose gene ontology compositions were similar to previous studies. However, despite our hypothesis, pregnancy specific proteins were not identified from the dental pulp of postpartum individuals (n = 5, 4–12 months postpartum). Although the dental pulp proteomes obtained from three individuals postpartum ≤6 months were distinct from those of other individuals by principal component analysis, their driving proteins were less evident. Although our hypothesis was not supported, sample collection, protein extraction, and mass spectrometry analysis could be improved to explore the forensic application of detecting pregnancy specific proteins in dental pulp.
2025-05-23 | PXD052602 | Pride
Project description:Background & Aims: Maternal liver exhibits robust adaptations to pregnancy to accommodate the metabolic needs of developing and growing placenta and fetus by largely unknown mechanisms. We found that achaete-scute homolog-like 1 (Ascl1), a basic helix-loop-helix transcription factor essential for neuronal development, is highly activated in maternal hepatocytes during the second half of gestation in mice. Methods: To investigate whether and how Ascl1 plays a pregnancy-dependent role, we deleted the Ascl1 gene specifically in maternal hepatocytes from mid-gestation until term. Results: As a result, we identified multiple Ascl1-dependent phenotypes. Maternal livers lacking Ascl1 exhibited aberrant hepatocyte structure, increased hepatocyte proliferation, enlarged hepatocyte size, reduced albumin production, and elevated release of liver enzymes, indicating maternal liver dysfunction. Simultaneously, maternal pancreas and spleen and the placenta displayed marked overgrowth; and the maternal ceca microbiome showed alterations in relative abundance of several bacterial subpopulations. Moreover, litters born from maternal hepatic Ascl1-deficient dams experienced abnormal postnatal growth after weaning, implying an adverse pregnancy outcome. Mechanistically, we found that maternal hepatocytes deficient for Ascl1 exhibited robust activation of insulin-like growth factor 2 expression, which may contribute to the Ascl1-dependent phenotypes widespread in maternal and uteroplacental compartments. Conclusion: In summary, we demonstrate that maternal liver, via activating Ascl1 expression, modulates the adaptations of maternal organs and the growth of the placenta to maintain a healthy pregnancy. Our studies reveal Ascl1 as a novel and critical regulator of the physiology of pregnancy.
2021-10-28 | GSE186620 | GEO
Project description:The objective of this study was to analyze genome-wide differential methylation patterns in maternal leukocyte DNA in early pregnant and non-pregnant states. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform. Transient widespread hypomethylation was found in early pregnancy as compared with the non-pregnant states. Methylation of nine genes was significantly different in early pregnancy compared to both postpartum and nulligravid states (< 10% False Discovery Rate). Early pregnancy may be characterized by widespread hypomethylation compared to non-pregnant states; there is no apparent permanent methylation imprint after a normal-term gestation. Nine potential candidate genes were identified as differentially methylated in early pregnancy and may play a role in the maternal adaptation to pregnancy. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform.
2012-10-15 | E-GEOD-37722 | biostudies-arrayexpress
Project description:Pregnancy imposes significant cardiovascular adaptations including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM have not been extensively examined in human hearts. We examined protein and metabolite expression in PPCM compared to familial dilated cardiomyopathy (DCM) and non-failing donors using unbiased quantitative mass spectrometry. Proteomics analysis identified uniquely downregulated proteins, such as SBSPON and TNS3, in PPCM relative to both DCM and donors. KEGG analysis of PPCM proteins identified key pathways associated with intracellular signalling cascades, protein folding and neurohormonal pathways that can directly impact the contractility of the heart. Metabolomics demonstrated uniquely expressed metabolites, such as upregulated homogentisate and deoxycholate, and downregulated lactate and alanine, along with reduced alanine, aspartate and glutamate metabolism are involved in the PPCM phenotype. Therefore, this study is the first to isolate unique molecular features underlying PPCM at the protein and metabolite level which may hold promise as future therapeutic candidate targets.
2025-05-07 | PXD055986 | Pride
Project description:Hepatic drug metabolism plays a key role in determining drug response and safety. Studies of drug metabolism generate valuable information about regulation of genes encoding drug-metabolizing enzymes and enzyme functions that are critical in developing dosing guideline. However, current knowledge is insufficient to support dosing guideline for pregnant women. Specifically, substrates of a major drug-metabolizing enzyme CYP2D6 show increased elimination during pregnancy, but the underlying mechanisms are completely unknown largely due to a lack of experimental models. Here, we introduce CYP2D6-humanized (Tg-CYP2D6) mice as an animal model where hepatic CYP2D6 expression is increased during pregnancy, recapitulating the clinically reported changes in CYP2D6-mediated drug metabolism. In these mice, pregnancy had minimal effects on the expression of hepatocyte nuclear factor (HNF) 4a, the transcription factor controlling basal CYP2D6 expression. Krüppel-like factor (KLF) 9 and small heterodimer partner (SHP) were found up- and down-regulated in Tg-CYP2D6 mouse livers during pregnancy, respectively. KLF9 enhanced HNF4a-mediated transactivation of the CYP2D6 promoter whereas SHP repressed it. Retinoic acid (RA), an endogenous compound that induces SHP, exhibited decreased hepatic levels during pregnancy. These results indicate that interplay among hepatic transcription factors HNF4a, SHP, and KLF9 underlies CYP2D6 induction during pregnancy, and that retinoic acid is a potential trigger. This is the first report on the mechanisms underlying CYP2D6 induction and illustrates the utility of humanized mice as an in vivo model to study altered drug disposition during pregnancy. Livers collected at pre-pregnancy, 21 days of pregnancy, and 7 days postpartum from CYP2D6-humanized mice.
2014-12-04 | E-GEOD-50166 | biostudies-arrayexpress