Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal1. In various pathophysiological conditions, erythrocyte life span is severely compromised, which threatens the organism with anemia and iron toxicity 2,3. Here we identify anon-demand mechanism specific to the liver that clears erythrocytes and recycles iron. We showthat Ly-6Chigh monocytes ingest stressed and senescent erythrocytes, accumulate in the liver, and differentiate to ferroportin 1 (FPN1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+ Tim-4neg macrophages are transient, reside alongside embryonically-derived Tim-4high Kuppfer cells, and depend on Csf1 and Nrf2. The spleenlikewise recruits iron-loaded Ly-6Chigh monocytes, but they do not differentiate into ironrecycling macrophages due to the suppressive action of Csf2, and are instead shuttled to the livervia coordinated chemotactic cues. Inhibiting this mechanism by preventing monocyte recruitment to the liver leads to kidney failure and liver damage. These observations identify the liver as the primary organ supporting emergency erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.
On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
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View SamplesIn order to examine the gene expression in the course of mosquito embryogenesis, microarray assays were performed on staged A. gambiae embryos, from fertilization to 52 hours of development (which is close to hatching at ~50 hours post-fertilization). RNA was extracted from staged embryos roughly every three hours after fertilization, and then hybridized to the A. gambiae transcriptome microarray.
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
No sample metadata fields
View SamplesWith particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR.
The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action.
Specimen part, Subject, Time
View SamplesRecently, we have shown that disturbed flow caused by partial ligation of mouse carotid artery rapidly induces endothelial dysfunction and atherosclerosis within two weeks. To understand the molecular mechanisms by which disturbed flow induces atherosclerosis, we carried out genome-wide microarray study using endothelial RNAs isolated from the flow-disturbed left and the contralateral right common carotid artery (LCA and RCA) in C57BL/6 mice.
Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow.
Sex, Specimen part, Time
View SamplesWhole-genome transcriptome assays were performed with isolated serosa from A. gambiae embryos. These assays identified a large number of genes implicated in the production of the larval cuticle. In D. melanogaster, these genes are activated just once during embryogenesis, during late stages where they are used for the production of the larval cuticle. Evidence is presented that the serosal cells secrete a dedicated serosal cuticle, which protects A. gambiae embryos from desiccation.
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
No sample metadata fields
View SamplesPurpose: The purpose of the study was to investigate the differential expression pattern of genes in Rag2 KO mice spleen compared to its wild type counterpart.
Microarray profiling of miRNA and mRNA expression in Rag2 knockout and wild-type mouse spleens.
No sample metadata fields
View SamplesBody size varies enormously among mammalian species. In small mammals, body growth is typically suppressed rapidly, within weeks, whereas in large mammals, growth is suppressed slowly, over years, allowing for a greater adult size. We recently reported evidence that body growth suppression in rodents is caused in part by a juvenile genetic program that occurs in multiple tissues simultaneously and involves the downregulation of a large set of growth-promoting genes. We hypothesized that this genetic program is conserved in large mammals but that its time course is evolutionarily modulated such that it plays out more slowly, allowing for more prolonged growth. Consistent with this hypothesis, using expression microarray analysis, we identified a set of genes that are downregulated with age in both juvenile sheep kidney and lung. This overlapping gene set was enriched for genes involved in cell proliferation and growth and showed striking similarity to a set of genes downregulated with age in multiple organs of the juvenile mouse and rat, indicating that the multiorgan juvenile genetic program previously described in rodents has been conserved in the 80 million years since sheep and rodents diverged in evolution. Using microarray and real-time PCR, we found that the pace of this program was most rapid in mice, more gradual in rats, and most gradual in sheep. The findings support the hypothesis that a growth-regulating genetic program is conserved among mammalian species but that its pace is modulated to allow more prolonged growth and therefore greater adult body size in larger mammals.
Evolutionary conservation and modulation of a juvenile growth-regulating genetic program.
Specimen part
View SamplesGeneration of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes.
Mouse liver repopulation with hepatocytes generated from human fibroblasts.
Specimen part
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