scholarly journals Ablation of SAMD1 in Mice Causes Failure of Angiogenesis, Embryonic Lethality

2022 ◽  
Author(s):  
Bruce Campbell ◽  
Sandra Engle ◽  
Patricia Bourassa ◽  
Robert Aiello
Keyword(s):  
Blood Cells ◽  
Normal Function ◽  
Cell Phenotype ◽  
Fab Fragment ◽  
Sterile Alpha Motif Domain ◽  
Atherosclerotic Lesions ◽  
Embryonic Lethal ◽  
Carotid Injury ◽  
Ldl Binding ◽  
Injury Models

Pathological retention of LDL in the intima is involved in atherosclerosis, although the retention mechanisms are not well-understood. Previously, we reported Sterile Alpha Motif Domain Containing 1 (SAMD1), a protein secreted by intimal smooth muscle cells in atherosclerotic lesions, appears to bind LDL in extracellular matrix around intimal cells. Fab-fragment inhibitors of apparently irreversible SAMD1/LDL binding reduced LDL retention in carotid injury models, but did not have a significant effect on early spontaneous lesion initiation. The normal function of SAMD1 is unknown, but it may have multiple epigenetic roles; our histology of mouse atherosclerosis models revealed extensive SAMD1 expression, possibly related to cell phenotype modulation and antigen presentation. For this report, we generated SAMD1-/-, SAMD1-/+, and SAMD1-/+ apoE-/- mice to further explore SAMD1's role in atherosclerosis. SAMD1 was found in tissues throughout the SAMD1+/+ and SAMD1-/+embryos. Homozygous loss of SAMD1 was embryonic lethal: at embryonic day 14, organs were partially developed and/or degraded; heads and brains were malformed; no blood vessels were observed; red blood cells were scattered and pooled, primarily near the embryo surface; and cell death was occurring. Development appeared normal in heterozygous SAMD1 embryos, but postnatal genotyping showed a reduced ability to thrive. Growth of atherosclerotic lesions in SAMD1-/+ apoE-/- after 35 weeks was not significantly less than in mice SAMD1+/+ apoE-/- mice.

scholarly journals Normal Functions of the Spleen Relative to Red Blood Cells: A Review

Blood ◽  
1959 ◽  
Vol 14 (4) ◽  
pp. 399-408 ◽  
Author(s):  
WILLIAM H. CROSBY
Keyword(s):  
Cell Surface ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Normal Function ◽  
Red Cells ◽  
Red Cell ◽  
Cell Production ◽  
Normal Functions ◽  
Normal Spleen ◽  
And Storage

Abstract During all the stages of a red cell’s life the normal spleen exerts a normal function. Eight of these functions have been considered: (1) erythropoiesis; (2) an effect upon red cell production; (3) an effect upon maturation of the red cell surface; (4) the reservoir function; (5) the "culling function"; (6) iron turnover and storage; (7) the "pitting function"; (8) destruction of old red cells.

scholarly journals Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis

Circulation ◽  
2020 ◽  
Vol 142 (21) ◽  
pp. 2045-2059 ◽  
Author(s):  
Gabriel F. Alencar ◽  
Katherine M. Owsiany ◽  
Santosh Karnewar ◽  
Katyayani Sukhavasi ◽  
Giuseppe Mocci ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Late Stage ◽  
Lineage Tracing ◽  
Stem Cell Marker ◽  
Cell Phenotype ◽  
Phenotypic Changes ◽  
Atherosclerotic Lesions ◽  
Single Cell Rna Sequencing

Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability. Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis. Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11 - , Lgals3 + population with a chondrocyte-like gene signature that was markedly reduced with SMC- Klf4 knockout. We observed that SMCs that activate Lgals3 compose up to two thirds of all SMC in lesions. However, initial activation of Lgals3 in these cells does not represent conversion to a terminally differentiated state, but rather represents transition of these cells to a unique stem cell marker gene–positive, extracellular matrix-remodeling, “pioneer” cell phenotype that is the first to invest within lesions and subsequently gives rise to at least 3 other SMC phenotypes within advanced lesions, including Klf4-dependent osteogenic phenotypes likely to contribute to plaque calcification and plaque destabilization. Conclusions: Taken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3 + osteogenic cells likely to be detrimental for late-stage atherosclerosis plaque pathogenesis.

NHLBI workshop report: endothelial cell phenotypes in heart, lung, and blood diseases

2001 ◽  
Vol 281 (5) ◽  
pp. C1422-C1433 ◽  
Author(s):  
Troy Stevens ◽  
Robert Rosenberg ◽  
William Aird ◽  
Thomas Quertermous ◽  
Frances L. Johnson ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Function ◽  
Cell Function ◽  
Normal Function ◽  
Cell Phenotype ◽  
Endothelial Cell Function ◽  
Blood Institute ◽  
Metabolic Role ◽  
And Function ◽  
Cell Phenotypes

Endothelium critically regulates systemic and pulmonary vascular function, playing a central role in hemostasis, inflammation, vasoregulation, angiogenesis, and vascular growth. Indeed, the endothelium integrates signals originating in the circulation with those in the vessel wall to coordinate vascular function. This highly metabolic role differs significantly from the historic view of endothelium, in which it was considered to be merely an inert barrier. New lines of evidence may further change our understanding of endothelium, in regard to both its origin and function. Embryological studies suggest that the endothelium arises from different sites, including angiogenesis of endothelium from macrovascular segments and vasculogenesis of endothelium from microcirculatory segments. These findings suggest an inherent phenotypic distinction between endothelial populations based on their developmental origin. Similarly, diverse environmental cues influence endothelial cell phenotype, critical to not only normal function but also the function of a diseased vessel. Consequently, an improved understanding of site-specific endothelial cell function is essential, particularly with consideration to environmental stimuli present both in the healthy vessel and in development of vasculopathic disease states. The need to examine endothelial cell phenotypes in the context of vascular function served as the basis for a recent workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI). This report is a synopsis of pertinent topics that were discussed, and future goals and research opportunities identified by the participants of the workshop are presented.

Expression of Proteins Controlling Transbilayer Movement of Plasma Membrane Phospholipids in the B Lymphocytes From a Patient With Scott Syndrome

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1707-1712 ◽  
Author(s):  
Quansheng Zhou ◽  
Peter J. Sims ◽  
Therese Wiedmer
Keyword(s):  
Plasma Membrane ◽  
Cell Lines ◽  
Blood Cells ◽  
Normal Function ◽  
Coagulation System ◽  
Functional Assay ◽  
Membrane Phospholipids ◽  
Normal Expression ◽  
American Society ◽  
Normal Controls

Scott syndrome is a rare inherited bleeding disorder in which platelets and other blood cells fail to promote normal assembly of the membrane-stabilized proteases of the plasma coagulation system. The defect in Scott blood cells is known to reflect inability to mobilize phosphatidylserine from inner plasma membrane leaflet to the cell surface in response to an elevation of Ca2+ at the endofacial surface. To gain insight into the molecular basis of this membrane defect, we examined the expression in Scott cells of plasma membrane proteins that have been implicated to participate in the accelerated transbilayer movement of plasma membrane PL. By both reverse transcriptase-polymerase chain reaction (RT-PCR) and functional assay, the level of expression of the multidrug resistance (MDR)1 and MDR3 P-glycoproteins in immortalized B-lymphoblast cell lines from the patient with Scott syndrome were indistinguishable from matched cell lines derived from normal controls. Whereas the plasma membrane of Scott cells are insensitive to activation of the plasma membrane PL scramblase pathway, it had been shown that PL scramblase protein isolated from detergent-solubilized Scott erythrocytes exhibits normal function when incorporated into proteoliposomes (Stout JG, Basse F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ: J Clin Invest 99:2232, 1997). Consistent with this finding in Scott erythrocytes, we found that Scott lymphoblasts expressed normal levels of PL scramblase mRNA and protein, and that the deduced sequence of PL scramblase in Scott cells is identical to that of normal controls. These data suggest that the defect in Scott syndrome is related either to aberrant posttranslational processing of the PL scramblase polypeptide or to a defect or deficiency in an unknown cofactor that is required for normal expression of plasma membrane PL scramblase function in situ, or alternatively, reflects the presence of a detergent-dissociable inhibitor of this pathway. © 1998 by The American Society of Hematology.

scholarly journals Porcine red blood cells express a polyagglutinable red blood cell phenotype

Transfusion ◽  
2005 ◽  
Vol 45 (6) ◽  
pp. 1035-1036 ◽  
Author(s):  
Jane L. Swanson ◽  
Laura Cooling
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Cell Phenotype

Expression of Proteins Controlling Transbilayer Movement of Plasma Membrane Phospholipids in the B Lymphocytes From a Patient With Scott Syndrome

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1707-1712 ◽  
Author(s):  
Quansheng Zhou ◽  
Peter J. Sims ◽  
Therese Wiedmer
Keyword(s):  
Plasma Membrane ◽  
Cell Lines ◽  
Blood Cells ◽  
Normal Function ◽  
Coagulation System ◽  
Functional Assay ◽  
Membrane Phospholipids ◽  
Normal Expression ◽  
American Society ◽  
Normal Controls

Abstract Scott syndrome is a rare inherited bleeding disorder in which platelets and other blood cells fail to promote normal assembly of the membrane-stabilized proteases of the plasma coagulation system. The defect in Scott blood cells is known to reflect inability to mobilize phosphatidylserine from inner plasma membrane leaflet to the cell surface in response to an elevation of Ca2+ at the endofacial surface. To gain insight into the molecular basis of this membrane defect, we examined the expression in Scott cells of plasma membrane proteins that have been implicated to participate in the accelerated transbilayer movement of plasma membrane PL. By both reverse transcriptase-polymerase chain reaction (RT-PCR) and functional assay, the level of expression of the multidrug resistance (MDR)1 and MDR3 P-glycoproteins in immortalized B-lymphoblast cell lines from the patient with Scott syndrome were indistinguishable from matched cell lines derived from normal controls. Whereas the plasma membrane of Scott cells are insensitive to activation of the plasma membrane PL scramblase pathway, it had been shown that PL scramblase protein isolated from detergent-solubilized Scott erythrocytes exhibits normal function when incorporated into proteoliposomes (Stout JG, Basse F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ: J Clin Invest 99:2232, 1997). Consistent with this finding in Scott erythrocytes, we found that Scott lymphoblasts expressed normal levels of PL scramblase mRNA and protein, and that the deduced sequence of PL scramblase in Scott cells is identical to that of normal controls. These data suggest that the defect in Scott syndrome is related either to aberrant posttranslational processing of the PL scramblase polypeptide or to a defect or deficiency in an unknown cofactor that is required for normal expression of plasma membrane PL scramblase function in situ, or alternatively, reflects the presence of a detergent-dissociable inhibitor of this pathway. © 1998 by The American Society of Hematology.

Attachment of Blood Cells onto ZrO2 and SiO2-Containing Glass

2005 ◽  
Vol 284-286 ◽  
pp. 671-674 ◽  
Author(s):  
Patricia Valério ◽  
Simeon Agathopoulos ◽  
A.J. Calado ◽  
M. Fatima Leite ◽  
Alfredo Goes
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Surface Roughness ◽  
Blood Cells ◽  
Normal Function ◽  
Material Surface ◽  
Sem Images ◽  
Material Interface ◽  
Human Whole Blood ◽  
Scanning Electron

Samples of zirconia and a bioinert SiO2-containing glass with different surface roughness were immersed into human whole blood for different settling times to investigate the adhesion and attachment of blood cells onto these materials. The cell/material interface was directly observed by scanning electron microscopy (SEM). The results indicate that the blood cells preserved their physiology and attaching capability regardless the type of material, surface roughness, and settling time. The SEM images strongly indicate the normal function of adhesion proteins.

scholarly journals The Ets2 Repressor Factor (Erf) Is Required for Effective Primitive and Definitive Hematopoiesis

2017 ◽  
Vol 37 (19) ◽  
Author(s):  
Ioanna Peraki ◽  
James Palis ◽  
George Mavrothalassitis
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Blood Cells ◽  
Fetal Liver ◽  
Normal Function ◽  
Severe Anemia ◽  
Hematopoietic Stem ◽  
Stem Cell Maintenance ◽  
Definitive Hematopoiesis ◽  
Cell Maintenance

ABSTRACT Erf is a gene for a ubiquitously expressed Ets DNA-binding domain-containing transcriptional repressor. Erf haploinsufficiency causes craniosynostosis in humans and mice, while its absence in mice leads to failed chorioallantoic fusion and death at embryonic day 10.5 (E10.5). In this study, we show that Erf is required in all three waves of embryonic hematopoiesis. Mice lacking Erf in the embryo proper exhibited severe anemia and died around embryonic day 14.5. Erf epiblast-specific knockout embryos had reduced numbers of circulating blood cells from E9.5 onwards, with the development of severe anemia by E14.5. Elimination of Erf resulted in both reduced and more immature primitive erythroblasts at E9.5 to E10.5. Reduced definitive erythroid colony-forming activity was found in the bloodstream of E10.5 embryos and in the fetal liver at E11.5 to E13.5. Finally, elimination of Erf resulted in impaired repopulation ability, indicating that Erf is necessary for hematopoietic stem cell maintenance or differentiation. We conclude that Erf is required for both primitive and erythromyeloid progenitor waves of hematopoietic stem cell (HSC)-independent hematopoiesis as well as for the normal function of HSCs.

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