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Developmental Cell Jul 2021In mammals, hematopoietic stem cells (HSCs) engage in hematopoiesis throughout adult life within the bone marrow, where they produce the mature cells necessary to... (Review)
Review
In mammals, hematopoietic stem cells (HSCs) engage in hematopoiesis throughout adult life within the bone marrow, where they produce the mature cells necessary to maintain blood cell counts and immune function. In the bone marrow and spleen, HSCs are sustained in perivascular niches (microenvironments) associated with sinusoidal blood vessels-specialized veins found only in hematopoietic tissues. Endothelial cells and perivascular leptin receptor stromal cells produce the known factors required to maintain HSCs and many restricted progenitors in the bone marrow. Various other cells synthesize factors that maintain other restricted progenitors or modulate HSC or niche function. Recent studies identified new markers that resolve some of the heterogeneity among stromal cells and refine the localization of restricted progenitor niches. Other recent studies identified ways in which niches regulate HSC function and hematopoiesis beyond growth factors. We summarize the current understanding of hematopoietic niches, review recent progress, and identify important unresolved questions.
Topics: Blood Vessels; Bone Marrow; Endothelial Cells; Hematopoiesis; Humans; Intercellular Signaling Peptides and Proteins; Receptors, Leptin; Spleen; Stem Cell Niche; Stem Cells
PubMed: 34146467
DOI: 10.1016/j.devcel.2021.05.018 -
PloS One 2018Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and...
Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar. A total of 15,040 lncRNA transcripts were identified among these samples. We found that the temporal expression pattern of lncRNAs was more restricted than observed for protein-coding genes. Time-series analysis showed two large modules for protein-coding genes and lncRNAs. The up-regulated module was enriched for genes related to immune and inflammatory function, while the down-regulated module was enriched for cell proliferation processes such as cell division and DNA replication. Co-expression networks indicated the functional relatedness between protein-coding genes and lncRNAs, which were enriched for similar functions over the series of time points examined. We identified numerous differentially expressed protein-coding genes and lncRNAs in all five developmental stages. Notably, ceruloplasmin precursor (CP), a protein-coding gene participating in antioxidant and iron transport processes, was differentially expressed in all stages. This study provides the first catalog of the developing pig spleen, and contributes to a fuller understanding of the molecular mechanisms underpinning mammalian spleen development.
Topics: Animals; Female; Gene Expression Profiling; Gene Library; Gene Regulatory Networks; Principal Component Analysis; RNA; RNA, Long Noncoding; RNA, Messenger; Sequence Analysis, RNA; Spleen; Swine; Transcriptome
PubMed: 29538394
DOI: 10.1371/journal.pone.0193552 -
Biochemical and Biophysical Research... Feb 2016NDRG4 is a member of the NDRG family (N-myc downstream-regulated gene), which is highly expressed in brain and heart. Previous studies showed that Ndrg1-deficient mice...
NDRG4 is a member of the NDRG family (N-myc downstream-regulated gene), which is highly expressed in brain and heart. Previous studies showed that Ndrg1-deficient mice exhibited a progressive demyelinating disorder of peripheral nerves and Ndrg4-deficient mice had spatial learning deficits and vulnerabilities to cerebral ischemia. Here, we report generation of Ndrg4 mutant alleles that exhibit several development defects different from those previously reported. Our homozygous mice showed growth retardation and postnatal lethality. Spleen and thymuses of Ndrg4(-/-) mice are considerably reduced in size from 3 weeks of age. Histological analysis revealed abnormal hyperkeratosis in the squamous foregut and abnormal loss of erythrocytes in the spleen of Ndrg4(-/-) mice. In addition, we observed an abnormal hind limb clasping phenotype upon tail suspension suggesting neurological abnormalities. Consistent to these abnormalities, Ndrg4 is expressed in smooth muscle cells of the stomach, macrophages of the spleen and neurons. Availability of the conditional allele for Ndrg4 should facilitate further detailed analyses of the potential roles of Ndrg4 in gut development, nervous system and immune system.
Topics: Animals; Digestive System Abnormalities; Erythrocytes; Fetal Growth Retardation; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nerve Tissue Proteins; Spleen; Survival Rate
PubMed: 26801554
DOI: 10.1016/j.bbrc.2016.01.096 -
Digestion 2021Before the discovery of immunological and haematological functions of the spleen, it had for centuries been considered to be a digestive organ of variable size with a... (Review)
Review
BACKGROUND
Before the discovery of immunological and haematological functions of the spleen, it had for centuries been considered to be a digestive organ of variable size with a role in the portal vein system and nutritional metabolism. In the 19th and 20th centuries, volume changes in the spleen related to nutrition were studied using plethysmographic measurements. Rhythmical and regulatory functions of the spleen were demonstrated in the haemodynamics of the splanchnic region and were described as a "hepatolienal pendulum," a "Windkessel function," or a "pressure compensation." These studies were mainly published in German-speaking countries and have not, as far as is known, been discussed in the English-speaking world so far.
SUMMARY
This review explores the historical development of the rhythmical regulatory function of the spleen in the splanchnic region. Older studies and results are followed up in the modern literature, wherever possible, up to the present. The clinical relevance is illustrated with portal hypertension (with congestive or hyperdynamic splenomegaly), coeliac disease, and chronic inflammatory bowel diseases (with functional hyposplenism). Key Message: The spleen's rhythmical regulatory function in nutrition is based on an autonomous rhythm comprising cycles of contractions and dilations of the spleen of around 1 min. These cycles can be influenced by sympathetically mediated single contractions with a release of pooled blood or by portal vein congestion. After food ingestion, the spleen responds either with contraction according to a vasomotor reaction or postprandial congestion with significant increases in volume. The spleen's rhythmical function is lost in the clinical picture of portal hypertension or in coeliac disease and chronic inflammatory bowel diseases. In the aforementioned gastrointestinal diseases, we recommend taking more account of the haemodynamics between the spleen, liver, and intestine. New innovative techniques for recording splenograms are required which, besides elastographic measurements of spleen stiffness, could offer an important tool for early detection, diagnosis, and therapeutic evaluation.
Topics: Humans; Hypertension, Portal; Portal Vein; Spleen; Splenomegaly
PubMed: 32408299
DOI: 10.1159/000507346 -
Poultry Science Aug 2020The spleen is the largest peripheral lymphoid organ and an important site of immune response, in which the blood-spleen barrier (BSB) plays a significant role to resist...
The spleen is the largest peripheral lymphoid organ and an important site of immune response, in which the blood-spleen barrier (BSB) plays a significant role to resist various pathogens. The BSB structure of duck spleen is different from that of chicken and mammals. However, no information about the development of BSB after the postembryonic age has been reported in ducks. The current study observed the spleen of 1, 7, 14, 21, 35, and 60-day-old ducks by light and electron microscopy to analyze the cellular structural development. The results showed that the spleen index was continuously increased from 1 to 14-day-old ducks. During their early age, the spleen of ducks showed no definite zone of white and red pulp, but the area of the white pulp was large compared to that of the red pulp. The diameter of the ellipsoid was constantly increased in up to 35-day-old duck spleen, while the periellipsoidal lymphatic sheath (PELS) and periarterial lymphatic sheath continuously developed after 1 D. The reticular fibers developed with age; their branching reached the ellipsoidal wall to show a developed framework in the BSB of 14-day-old ducks. After 7 D, the endothelial cells of the sheathed capillary showed a typical cuboidal shape; between these cells, the gaps increased as age advanced, while the thickness of the basement membrane and collagen fibers increased in 35-day-old ducks. The mechanical filtration function of BSB by intravenous injection showed a 1-layer ring of carbon particles restricted in the white pulp in 1-day-old duck spleen; however, in 14 to 60 D, these particles were restricted in the ellipsoid and PELS, forming 2-layer rings of carbon particles. Collectively, the cellular features of the duck BSB developed up to 35 D of postembryonic age to perform their immune function.
Topics: Animals; Ducks; Endothelial Cells; Immunity; Spleen
PubMed: 32731968
DOI: 10.1016/j.psj.2020.05.012 -
Experimental and Molecular Pathology Oct 2021Stem cell factor (SCF) is an essential cytokine during development and is necessary for gametogenesis, hematopoiesis, mast cell development, stem cell function, and...
Stem cell factor (SCF) is an essential cytokine during development and is necessary for gametogenesis, hematopoiesis, mast cell development, stem cell function, and melanogenesis. Here, we measure SCF concentration and distribution in adult humans and mice using gene expression analysis, tissue staining, and organ protein lysates. We demonstrate continued SCF expression in many cell types and tissues into adulthood. Tissues with high expression in adult humans included stomach, spleen, kidney, lung, and pancreas. In mice, we found high SCF expression in the esophagus, ovary, uterus, kidney, and small intestine. Future studies may correlate our findings of increased, organ-specific SCF concentrations within adult tissues with increased risk of SCF/CD117-related disease.
Topics: Adult; Animals; Cell Differentiation; Gametogenesis; Gene Expression Regulation, Developmental; Hematopoiesis; Humans; Kidney; Lung; Mast Cells; Mice; Pancreas; Proto-Oncogene Proteins c-kit; Spleen; Stem Cell Factor; Stem Cells; Stomach; Tissue Distribution
PubMed: 34450114
DOI: 10.1016/j.yexmp.2021.104678 -
Veterinary Pathology Jan 2017Splenitis is uncommonly reported in dogs. Herein, the authors describe its prevalence, clinical findings and outcomes, histologic patterns, and causes. Splenic samples...
Splenitis is uncommonly reported in dogs. Herein, the authors describe its prevalence, clinical findings and outcomes, histologic patterns, and causes. Splenic samples of dogs diagnosed with splenitis between 2005 and 2013 were collected and stained with hematoxylin and eosin, Gram, green-Gram, Giemsa, periodic acid-Schiff, and Ziehl-Neelsen. Samples were processed for polymerase chain reaction (PCR) to detect bacteria, fungi, and protozoa ( Leishmania infantum, Hepatozoon canis). Thirty-three of 660 splenic samples (5%) had splenitis. Clinical findings and outcomes were available in 19 dogs (58%); 49% had weakness, 33% had fever, and 84% survived. The most frequent inflammatory patterns included purulent splenitis (27%), pyogranulomatous splenitis (24%), and neutrophilic perisplenitis (15%). One dog had a putative diagnosis of primary splenitis; in 8 dogs, microorganisms were identified histologically or by PCR in the spleen without obvious comorbidities. Twenty-four dogs (73%) had concurrent diseases; a permissive role in the development of splenitis was suspected in 21 of these cases. Histologic examination identified the cause of splenitis in 10 dogs. Bacteria were identified by PCR in 23 cases, but the bacteria were confirmed histologically in only 6 of these. Leishmania was detected with PCR in 6 dogs. Leishmania was identified in 1 dog and H. canis in another histologically, but both were PCR negative. Fungi were identified in 8 spleens by PCR and in 1 by histology. This study suggests that splenitis is uncommon in dogs and is frequently associated with systemic diseases. Prognosis is favorable in most cases. Identification of bacteria, fungi, and protozoa in the spleens of affected dogs with PCR should be interpreted cautiously, because the findings are not confirmed histologically in many cases.
Topics: Animals; Biopsy; Dog Diseases; Dogs; Male; Polymerase Chain Reaction; Spleen; Splenic Diseases
PubMed: 27337982
DOI: 10.1177/0300985816653989 -
The Korean Journal of Parasitology Oct 2019Toxoplasma gondii infection induces parasite infiltration and apoptosis in the spleen. However, dose-dependent parasite infiltration, apoptosis, body weight alternations...
Toxoplasma gondii infection induces parasite infiltration and apoptosis in the spleen. However, dose-dependent parasite infiltration, apoptosis, body weight alternations and survival in mice remain largely unknown. In this study, mice were intraperitoneally infected with 10, 30 or 100 tachyzoites of T. gondii, respectively. Parasite infiltration and apoptosis in the spleen were analyzed on days 3, 7, and 9 post-infection by immunohistochemistry and flow cytometry. Significantly higher levels of T. gondii infiltration and apoptosis in the spleen were found in 30 and 100 tachyzoites infected mice compared to 10 tachyzoites infected mice on days 7 and 9 post-infection. Although 30 and 100 tachyzoites infected mice showed significant body weight loss compared to 10 tachyzoites infected mice, all of the 100, 30, and 10 tachyzoites infected mice died by days 12, 15, and 17, each respectively. Interestingly, T. gondii infiltration in 10 tachyzoites infected mice were limited to capsule area of the spleen on day 9 post-infection. Several areas of parasite infiltrations were found in the 30 tachyzoites infected mice, where noticeable levels of splenic capsule de-adhesion occurred. These results indicated that parasite infiltration and apoptosis in the spleen, as well as body weight loss (survival) are closely correlated with infection dosage. The level of T. gondii infiltration and apoptosis in the spleen and splenic de-adhesion were dependent on the parasite dose.
Topics: Animals; Apoptosis; Female; Humans; Life Cycle Stages; Mice; Mice, Inbred BALB C; Spleen; Toxoplasma; Toxoplasmosis
PubMed: 31715697
DOI: 10.3347/kjp.2019.57.5.537 -
Brain, Behavior, and Immunity Sep 1991The ontogeny of spleen cell proliferation to T and B cell mitogens and immunoglobulin secretion, measured in vitro, was examined in neonatally sympathectomized Fischer... (Review)
Review
The ontogeny of spleen cell proliferation to T and B cell mitogens and immunoglobulin secretion, measured in vitro, was examined in neonatally sympathectomized Fischer 344 (F344) rats, administered the neurotoxic drug 6-hydroxydopamine (6-OHDA) from 1 to 3 days of age. Compared to cells from age-matched controls, spleen cells from neonatally sympathectomized animals, aged 7-14 days, exhibited a shift in the proliferative response to the T cell mitogen, concanavalin A (Con A), with reduced proliferation in the presence of low doses of Con A, but increased proliferation with higher doses. During the same period, from 7 to 14 days, the B cell mitogen STM/DxS inhibited proliferation by spleen cells from all rats, and no effect of sympathectomy was observed. As adult-like patterns of mitogen responsiveness emerged from 21 to 42 days of age, neonatally sympathectomized rats showed reduced proliferative responses of both T and B cells. This effect dissipated by 56 days of age. Polyclonal immunoglobulin (Ig) production by B cells was assessed in vitro in the presence or absence of STM/DxS. Neonatal sympathectomy resulted in reduced spontaneous IgM production throughout development. From 28 to 42 days of age, when mitogen-triggered IgM secretion first developed, neonatal sympathectomy decreased the magnitude of the response. By 56 days of age, mitogen-induced IgM secretion was no longer affected by sympathectomy, similar to the proliferative response. Gender influenced the time course of sympathectomy-induced changes in spleen cell proliferation and differentiation; however, the magnitude and direction of these changes were similar in both males and females. Desipramine, administered prior to 6-OHDA, prevented both sympathetic denervation and the 6-OHDA-induced changes in spleen cell responsiveness. This indicates that the alterations in immune function were dependent on NA nerve fiber destruction and were not simply the result of direct 6-OHDA action on other cells. The results of this study suggest that sympathetic innervation may play an important potentiating role in the development of the lymphoid system, through effects on lymphocyte proliferation and differentiation.
Topics: Animals; Animals, Newborn; Antibody Formation; Cell Differentiation; Cell Division; Female; Immunoglobulin M; Lymphocyte Activation; Lymphocyte Subsets; Male; Mitogens; Norepinephrine; Organ Specificity; Oxidopamine; Rats; Rats, Inbred F344; Sex Factors; Spleen; Sympathectomy, Chemical
PubMed: 1954402
DOI: 10.1016/0889-1591(91)90021-2 -
Immunogenetics Feb 2021The function of a tissue is determined by its construction and cellular composition. The action of different genes can thus only be understood properly when seen in the... (Review)
Review
The function of a tissue is determined by its construction and cellular composition. The action of different genes can thus only be understood properly when seen in the context of the environment in which they are expressed and function. We now experience a renaissance in morphological research in fish, not only because, surprisingly enough, large structures have remained un-described until recently, but also because improved methods for studying morphological characteristics in combination with expression analysis are at hand. In this review, we address anatomical features of teleost immune tissues. There are approximately 30,000 known teleost fish species and only a minor portion of them have been studied. We aim our review at the Atlantic salmon (Salmo salar) and other salmonids, but when applicable, we also present information from other species. Our focus is the anatomy of the kidney, thymus, spleen, the interbranchial lymphoid tissue (ILT), the newly discovered salmonid cloacal bursa and the naso-pharynx associated lymphoid tissue (NALT).
Topics: Animals; Fishes; Gills; Kidney; Lymphoid Tissue; Nasopharynx; Salmo salar; Spleen; Thymus Gland
PubMed: 33426583
DOI: 10.1007/s00251-020-01196-0