Identity of cells containing apolipoprotein B messenger RNA, in 6- to 12-week postfertilization human embryos

Development ◽  
1987 ◽  
Vol 100 (1) ◽  
pp. 83-93
Author(s):  
B Hopkins ◽  
AL Brice ◽  
PN Schofield ◽  
FE Baralle ◽  
CF Graham
Keyword(s):  
Apolipoprotein B ◽  
Messenger Rna ◽  
Early Stage ◽  
Fetal Liver ◽  
Cdna Probe ◽  
Fetal Brain ◽  
Cell Types ◽  
Human Embryos ◽  
Apo B ◽  
Yolk Sack

Apolipoprotein B (Apo B) mRNA has been localized by in situ hybridization to various cell types in the liver, gut and yolk sack of the 6- to 12-week postfertilization human conceptus. In the fetal liver it is probable that the immature hepatocytes contain Apo B mRNA. In the yolk sack, the Apo B cDNA probe hybridizes mainly to the large endodermal cells and in the fetal gut the epithelium seems responsible for the majority of Apo B mRNA production. The fetal brain did not show any detectable hybridization to the Apo B probe. Unlike the situation seen in the adult, immunoprecipitation experiments demonstrated that only the B100 form of the protein was synthesized and secreted by the liver, gut and yolk sack at this early stage of human development.

Different Roles of Glycosylphosphatidylinositol in Various Hematopoietic Cells as Revealed by a Mouse Model of Paroxysmal Nocturnal Hemoglobinuria

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 2963-2970 ◽  
Author(s):  
Y. Murakami ◽  
T. Kinoshita ◽  
Y. Maeda ◽  
T. Nakano ◽  
H. Kosaka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Clone ◽  
Early Stage ◽  
Fetal Liver ◽  
Cell Types ◽  
Gpi Anchor ◽  
Hematopoietic Stem ◽  
Linked Gene

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have one or a few clones of mutant hematopoietic stem cells defective in glycosylphosphatidylinositol (GPI) synthesis as a result of somatic mutation in the X-linked gene PIG-A. The mutant stem cell clone dominates hematopoiesis by a mechanism that is unclear. To test whether a lack of multiple GPI-anchored proteins results in dysregulation and expansion of stem cells, we generated mice in which GPI-anchor negative cells are present only in the hematopoietic system. We transplanted lethally irradiated mice with female fetal liver cells bearing one allele of the Piga gene disrupted by conditional gene targeting. Because of the X-chromosome inactivation, a significant fraction of the hematopoietic stem cells in fetal livers was GPI-anchor negative. In the transplanted mice, cells of all hematopoietic lineages contained GPI-anchor negative cells. The percentage of GPI-anchor negative cells was much higher in T lymphocytes including immature thymocytes than in other cell types, suggesting a regulatory role for GPI-anchored proteins at an early stage of T-lymphocyte development. However, the proportions of GPI-anchor negative cells in various blood cell lineages were stable over a period of 42 weeks, indicating thatPiga mutation alone does not account for the dominance of the mutant stem cells and that other phenotypic changes are involved in pathogenesis of PNH.

DHA supplementation during prenatal ethanol exposure alters the expression of fetal rat liver genes involved in oxidative stress regulation

2019 ◽  
Vol 44 (7) ◽  
pp. 744-750 ◽  
Author(s):  
Bradley A. Feltham ◽  
Xavier L. Louis ◽  
Fatemeh Ramezani Kapourchali ◽  
Michael N.A. Eskin ◽  
Miyoung Suh
Keyword(s):  
Messenger Rna ◽  
Fetal Alcohol Spectrum Disorders ◽  
Fetal Liver ◽  
Fetal Brain ◽  
Signs And Symptoms ◽  
Liver Weight ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Sprague Dawley ◽  
Gene Expressions

Prenatal ethanol (EtOH) exposure is known to induce adverse effects on fetal brain development. Docosahexaenoic acid (DHA) has been shown to alleviate these effects by up-regulating antioxidant mechanisms in the brain. The liver is the first organ to receive enriched blood after placental transport. Therefore, it could be negatively affected by EtOH, but no studies have assessed the effects of DHA on fetal liver. This study examined the effects of maternal DHA intake on DHA status and gene expression of key enzymes of the glutathione antioxidant system in the fetal liver after prenatal EtOH exposure. Pregnant Sprague–Dawley dams were intubated with EtOH for the first 10 days of pregnancy, while being fed a control or DHA-supplemented diet. Fetal livers were collected at gestational day 20, and free fatty acids and phospholipid profile, as well as glutathione reductase (GR) and glutathione peroxidase-1 (GPx1) gene expressions, were assessed. Prenatal EtOH exposure increased fetal liver weight, whereas maternal DHA supplementation decreased fetal liver weight. DHA supplementation increased fetal liver free fatty acid and phospholipid DHA independently of EtOH. GR and GPx1 messenger RNA (mRNA) expressions were significantly increased and decreased, respectively, in the EtOH-exposed group compared with all other groups. Providing DHA normalized GR and GPx1 mRNA expression to control levels. This study shows that maternal DHA supplementation alters the expression of fetal liver genes involved in the glutathione antioxidative system during prenatal EtOH exposure. The fetal liver may play an important role in mitigating the signs and symptoms of fetal alcohol spectrum disorders in affected offspring.

scholarly journals IFNγ-Producing γ/δ T Cells Accumulate in the Fetal Brain Following Intrauterine Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Emma L. Lewis ◽  
Natalia Tulina ◽  
Lauren Anton ◽  
Amy G. Brown ◽  
Paige M. Porrett ◽  
...  
Keyword(s):  
T Cells ◽  
Reproductive Tract ◽  
Immune Cell ◽  
Fetal Liver ◽  
Fetal Brain ◽  
Cell Types ◽  
Autism Spectrum ◽  
Specific Cell ◽  
Term Infants ◽  
Cellular Immune

Intrauterine inflammation impacts prenatal neurodevelopment and is linked to adverse neurobehavioral outcomes ranging from cerebral palsy to autism spectrum disorder. However, the mechanism by which a prenatal exposure to intrauterine inflammation contributes to life-long neurobehavioral consequences is unknown. To address this gap in knowledge, this study investigates how inflammation transverses across multiple anatomic compartments from the maternal reproductive tract to the fetal brain and what specific cell types in the fetal brain may cause long-term neuronal injury. Utilizing a well-established mouse model, we found that mid-gestation intrauterine inflammation resulted in a lasting neutrophil influx to the decidua in the absence of maternal systemic inflammation. Fetal immunologic changes were observed at 72-hours post-intrauterine inflammation, including elevated neutrophils and macrophages in the fetal liver, and increased granulocytes and activated microglia in the fetal brain. Through unbiased clustering, a population of Gr-1+ γ/δ T cells was identified as the earliest immune cell shift in the fetal brain of fetuses exposed to intrauterine inflammation and determined to be producing high levels of IFNγ when compared to γ/δ T cells in other compartments. In a case-control study of term infants, IFNγ was found to be elevated in the cord blood of term infants exposed to intrauterine inflammation compared to those without this exposure. Collectively, these data identify a novel cellular immune mechanism for fetal brain injury in the setting of intrauterine inflammation.

Different Roles of Glycosylphosphatidylinositol in Various Hematopoietic Cells as Revealed by a Mouse Model of Paroxysmal Nocturnal Hemoglobinuria

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 2963-2970 ◽  
Author(s):  
Y. Murakami ◽  
T. Kinoshita ◽  
Y. Maeda ◽  
T. Nakano ◽  
H. Kosaka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Clone ◽  
Early Stage ◽  
Fetal Liver ◽  
Cell Types ◽  
Gpi Anchor ◽  
Hematopoietic Stem ◽  
Linked Gene

Abstract Patients with paroxysmal nocturnal hemoglobinuria (PNH) have one or a few clones of mutant hematopoietic stem cells defective in glycosylphosphatidylinositol (GPI) synthesis as a result of somatic mutation in the X-linked gene PIG-A. The mutant stem cell clone dominates hematopoiesis by a mechanism that is unclear. To test whether a lack of multiple GPI-anchored proteins results in dysregulation and expansion of stem cells, we generated mice in which GPI-anchor negative cells are present only in the hematopoietic system. We transplanted lethally irradiated mice with female fetal liver cells bearing one allele of the Piga gene disrupted by conditional gene targeting. Because of the X-chromosome inactivation, a significant fraction of the hematopoietic stem cells in fetal livers was GPI-anchor negative. In the transplanted mice, cells of all hematopoietic lineages contained GPI-anchor negative cells. The percentage of GPI-anchor negative cells was much higher in T lymphocytes including immature thymocytes than in other cell types, suggesting a regulatory role for GPI-anchored proteins at an early stage of T-lymphocyte development. However, the proportions of GPI-anchor negative cells in various blood cell lineages were stable over a period of 42 weeks, indicating thatPiga mutation alone does not account for the dominance of the mutant stem cells and that other phenotypic changes are involved in pathogenesis of PNH.

scholarly journals Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ivette Cruz-Bautista ◽  
Alicia Huerta-Chagoya ◽  
Hortensia Moreno-Macías ◽  
Rosario Rodríguez-Guillén ◽  
María Luisa Ordóñez-Sánchez ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Rare Variants ◽  
Regulatory Proteins ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Apo B ◽  
Independent Components ◽  
Apolipoprotein A

Abstract Background Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. Methods This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. Results Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. Conclusions The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.

scholarly journals First blood: the endothelial origins of hematopoietic progenitors

Angiogenesis ◽  
2021 ◽  
Author(s):  
Giovanni Canu ◽  
Christiana Ruhrberg
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Fetal Liver ◽  
Cell Types ◽  
Yolk Sac ◽  
Vascular Endothelial ◽  
Hematopoietic Stem ◽  
Close Proximity ◽  
Clinical Interest

AbstractHematopoiesis in vertebrate embryos occurs in temporally and spatially overlapping waves in close proximity to blood vascular endothelial cells. Initially, yolk sac hematopoiesis produces primitive erythrocytes, megakaryocytes, and macrophages. Thereafter, sequential waves of definitive hematopoiesis arise from yolk sac and intraembryonic hemogenic endothelia through an endothelial-to-hematopoietic transition (EHT). During EHT, the endothelial and hematopoietic transcriptional programs are tightly co-regulated to orchestrate a shift in cell identity. In the yolk sac, EHT generates erythro-myeloid progenitors, which upon migration to the liver differentiate into fetal blood cells, including erythrocytes and tissue-resident macrophages. In the dorsal aorta, EHT produces hematopoietic stem cells, which engraft the fetal liver and then the bone marrow to sustain adult hematopoiesis. Recent studies have defined the relationship between the developing vascular and hematopoietic systems in animal models, including molecular mechanisms that drive the hemato-endothelial transcription program for EHT. Moreover, human pluripotent stem cells have enabled modeling of fetal human hematopoiesis and have begun to generate cell types of clinical interest for regenerative medicine.

scholarly journals An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot S. Virdee ◽  
Nipun Saini ◽  
Colin D. Kay ◽  
Andrew P. Neilson ◽  
Sze Ting Cecilia Kwan ◽  
...  
Keyword(s):  
Phenolic Acids ◽  
Fetal Liver ◽  
Prenatal Alcohol Exposure ◽  
Fetal Brain ◽  
Principal Component ◽  
Alcohol Exposure ◽  
Maternal Plasma ◽  
Cognitive Disability ◽  
Fetal Alcohol ◽  
Network Analyses

AbstractPrenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE model, we performed untargeted metabolome analyses upon the maternal–fetal dyad at gestational day 17.5. Hierarchical clustering by principal component analysis and Pearson’s correlation of maternal plasma (813 metabolites) both identified MDPs as significant predictors for PAE. The majority were phenolic acids enriched in PAE. Correlational network analyses revealed that alcohol altered plasma MDP-metabolite relationships, and alcohol-exposed maternal plasma was characterized by a subnetwork dominated by phenolic acids. Twenty-nine MDPs were detected in fetal liver and sixteen in fetal brain, where their impact is unknown. Several of these, including 4-ethylphenylsulfate, oxindole, indolepropionate, p-cresol sulfate, catechol sulfate, and salicylate, are implicated in other neurological disorders. We conclude that MDPs constitute a characteristic biosignature that distinguishes PAE. These MDPs are abundant in human plasma, where they influence physiology and disease. Their altered abundance here may reflect alcohol’s known effects on microbiota composition and gut permeability. We propose that the maternal microbiome and its MDPs are a previously unrecognized influence upon the pathologies that typify PAE.

scholarly journals Determination of the molecular mass of apolipoprotein B-100 A chemical approach

1986 ◽  
Vol 239 (3) ◽  
pp. 777-780 ◽  
Author(s):  
C Y Yang ◽  
F S Lee ◽  
L Chan ◽  
D A Sparrow ◽  
J T Sparrow ◽  
...  
Keyword(s):  
Molecular Mass ◽  
Apolipoprotein B ◽  
Cell Surface Receptor ◽  
Specific Cell ◽  
Apo B ◽  
Chemical Approach ◽  
Surface Receptor ◽  
Cnbr Cleavage ◽  
Specific Cell Surface

Apolipoprotein B-100 (apo B-100) is the protein ligand in low-density lipoproteins that binds to a specific cell-surface receptor. Its molecular mass has been a subject of controversy. We have determined the molecular mass of the protein by a chemical approach. After complete CNBr cleavage, the C-terminal fragment of apo B-100 was purified by reverse-phase h.p.l.c. Amino acid N- and C-terminal analyses confirm that this peptide represents the C-terminal peptide as deduced from the DNA sequence of a human apo B-100 cDNA clone. A chemically synthesized peptide was used to determine the recovery of the peptide (74.72%). On the basis of these data, the molecular mass of apo B-100 was determined to be 496.82 +/- 24.84 kDa.

Regulation of N-myc gene expression: use of an adenovirus vector to demonstrate posttranscriptional control

1990 ◽  
Vol 10 (12) ◽  
pp. 6700-6708
Author(s):  
L E Babiss ◽  
J M Friedman
Keyword(s):  
Recombinant Adenovirus ◽  
Wilms Tumor ◽  
Fetal Brain ◽  
Adenovirus Vector ◽  
Cell Types ◽  
Adult Brain ◽  
Posttranscriptional Control ◽  
Equivalent Rate ◽  
Myc Gene ◽  
Recombinant Adenovirus Vector

We present evidence that differences in the levels of N-myc mRNA among different cell types are the result of posttranscriptional control. First, we noted that while steady-state mouse N-myc mRNA could be detected only in fetal mouse brain, it was transcribed at an equivalent rate in adult brain, liver, spleen, and placenta and in fetal brain. Similarly, the human N-myc gene was transcribed at an equivalent rate in HeLa cells, which do not accumulate this RNA in the cytoplasm, and cell lines G401 (a Wilms tumor-derived cell line) and SKNMc (established from a primitive neuroepithelioma), which do express N-myc RNA. As expected, the N-myc promoter functioned at equivalent rates, as demonstrated by the level of a reporter gene, when introduced into these cell types by using a recombinant adenovirus vector. The suggestion that posttranscriptional mechanisms control the level of this RNA was supported by the observation that sequences in the N-myc third exon specifically decreased the level of E1A mRNA when these sequences were placed downstream of the E1A promoter in a recombinant adenovirus. Finally, we further localized these sequences to a 600-bp fragment of the third exon by introducing various subclones of this sequence downstream of the E1A promoter in both viral and plasmid vectors.

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