Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4055-4063 ◽  
Author(s):  
Vanta J. Jokubaitis ◽  
Lidia Sinka ◽  
Rebecca Driessen ◽  
Genevieve Whitty ◽  
David N. Haylock ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Blood Cells ◽  
Fetal Liver ◽  
Converting Enzyme ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Nonobese Diabetic ◽  
Human Hscs ◽  
Ventral Wall

Abstract Previous studies revealed that mAb BB9 reacts with a subset of CD34+ human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map BB9 expression throughout hematopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and surrounding endothelial cells are BB9+. Thereafter, BB9 is expressed by primitive hematopoietic cells in fetal liver and in umbilical cord blood (UCB). BB9+CD34+ UCB cells transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice contribute 10-fold higher numbers of multilineage blood cells than their CD34+BB9− counterparts and contain a significantly higher incidence of SCID-repopulating cells than the unfractionated CD34+ population. Protein microsequencing of the 160-kDa band corresponding to the BB9 protein established its identity as that of somatic angiotensin-converting enzyme (ACE). Although the role of ACE on human HSCs remains to be determined, these studies designate ACE as a hitherto unrecognized marker of human HSCs throughout hematopoietic ontogeny and adulthood.

scholarly journals Cited2 is required for normal hematopoiesis in the murine fetal liver

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2889-2898 ◽  
Author(s):  
Yu Chen ◽  
Peter Haviernik ◽  
Kevin D. Bunting ◽  
Yu-Chung Yang
Keyword(s):  
Fetal Liver ◽  
Liver Cells ◽  
Cathepsin G ◽  
Molecular Regulation ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Fetal Liver Cells ◽  
B Lymphoid ◽  
First Time

Abstract Cited2 (cAMP-responsive elementbinding protein [CBP]/p300-interacting transactivators with glutamic acid [E] and aspartic acid [D]–rich tail 2) is a newly identified transcriptional modulator. Knockout of the Cited2 gene results in embryonic lethality with embryos manifesting heart and neural tube defects. Cited2−/− fetal liver displayed significant reduction in the numbers of Lin−c-Kit+Sca-1+ cells, Lin−c-Kit+ cells, and progenitor cells of different lineages. Fetal liver cells from Cited2−/− embryos gave rise to markedly reduced number of colonies in the colony-forming unit assay. Primary and secondary transplantation studies showed significantly compromised reconstitution of T-lymphoid, B-lymphoid, and myeloid lineages in mice that received a transplant of Cited2−/− fetal liver cells. Competitive reconstitution experiments further showed that fetal liver hematopoietic stem cell (HSC) function is severely impaired due to Cited2 deficiency. Microarray analysis showed decreased expression of Wnt5a and a panel of myeloid molecular markers such as PRTN3, MPO, Neutrophil elastase, Cathepsin G, and Eosinophil peroxidase in Cited2−/− fetal livers. Decreased expression of Bmi-1, Notch1, LEF-1, Mcl-1, and GATA2 was also observed in Cited2−/− Lin−c-Kit+ cells. The present study uncovers for the first time a novel role of Cited2 in the maintenance of hematopoietic homeostasis during embryogenesis and thus provides new insights into the molecular regulation of hematopoietic development.

scholarly journals Angiotensin-converting enzyme (CD143) specifies emerging lympho-hematopoietic progenitors in the human embryo

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3712-3723 ◽  
Author(s):  
Lidia Sinka ◽  
Katia Biasch ◽  
Ibrahim Khazaal ◽  
Bruno Péault ◽  
Manuela Tavian
Keyword(s):  
Stem Cells ◽  
Angiotensin Converting Enzyme ◽  
Hematopoietic Stem Cells ◽  
Human Embryo ◽  
Fetal Liver ◽  
Converting Enzyme ◽  
Hematopoietic Progenitors ◽  
Adult Type ◽  
Hematopoietic Stem ◽  
Adult Human

Abstract Adult-type lympho-myeloid hematopoietic progenitors are first generated in the aorta-gonad-mesonephros region between days 27 and 40 of human embryonic development, but an elusive blood forming potential is present earlier in the underlying splanchnopleura. In the present study, we show that angiotensin-converting enzyme (ACE, also known as CD143), a recently identified cell-surface marker of adult human hematopoietic stem cells, is already expressed in all presumptive and developing blood-forming tissues of the human embryo and fetus: para-aortic splanchnopleura, yolk sac, aorta-gonad-mesonephros, liver, and bone marrow (BM). Fetal liver and BM-derived CD34+ACE+ cells, but not CD34+ACE− cells, are endowed with long-term culture-initiating cell potential and sustain multilineage hematopoietic cell engraftment when transplanted into NOD/SCID mice. Furthermore, from 23-26 days of development, ACE expression characterizes rare CD34−CD45− cells concentrated in the hemogenic portion of the para-aortic splanchnopleura. ACE+ cells sorted from the splanchnopleura generated colonies of hematopoietic cells more than 40 times more frequently than ACE− cells. These data suggest that, in addition to being a marker of adult human hematopoietic stem cells, ACE identifies embryonic mesodermal precursors responsible for definitive hematopoiesis, and we propose that this enzyme is involved in the regulation of human blood formation.

Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular complications

2013 ◽  
Vol 126 (7) ◽  
pp. 471-482 ◽  
Author(s):  
Vaibhav B. Patel ◽  
Nirmal Parajuli ◽  
Gavin Y. Oudit
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Converting Enzyme ◽  
Vascular Function ◽  
Systolic Dysfunction ◽  
Cardiovascular Complications ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Obesity And Diabetes

Diabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic proportions. Therefore urgent actions are needed to stem the tide of diabetes which entails new prevention and treatment tools. Clinical and pharmacological studies have demonstrated that AngII (angiotensin II), the major effector peptide of the RAS (renin–angiotensin system), is a critical promoter of insulin resistance and diabetes mellitus. The role of RAS and AngII has been implicated in the progression of diabetic cardiovascular complications and AT1R (AngII type 1 receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown clinical benefits. ACE2, the recently discovered homologue of ACE, is a monocarboxypeptidase which converts AngII into Ang-(1–7) [angiotensin-(1–7)] which, by virtue of its actions on the MasR (Mas receptor), opposes the effects of AngII. In animal models of diabetes, an early increase in ACE2 expression and activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic dysfunction and impaired vascular function. In the present review, we will discuss the role of the RAS in the pathophysiology and treatment of diabetes and its complications with particular emphasis on potential benefits of the ACE2/Ang-(1–7)/MasR axis activation.

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