Existence and Differential Changes of Peptidylarginine Deiminase Type II in Mouse Yolk-Sac Erythroid Cells

Abstract Acute chicken leukemia retroviruses, because of their capacity to readily transform hematopoietic cells in vitro, are ideal models to study the mechanisms governing the cell-type specificity of oncoproteins. Here we analyzed the transformation specificity of 2 acute chicken leukemia retroviruses, the Myb-Ets– encoding E26 virus and the ErbA/ErbB-encoding avian erythroblastosis virus (AEV). While cells transformed by E26 are multipotent (designated “MEP” cells), those transformed by AEV resemble erythroblasts. Using antibodies to separate subpopulations of precirculation yolk sac cells, both viruses were found to induce the proliferation of primitive erythroid progenitors within 2 days of infection. However, while AEV induced a block in differentiation of the cells, E26 induced a gradual shift in their phenotype and the acquisition of the potential for multilineage differentiation. These results suggest that the Myb-Ets oncoprotein of the E26 leukemia virus converts primitive erythroid cells into proliferating definitive-type multipotent hematopoietic progenitors.

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Control of ribosomal RNA maturation in differentiating yolk sac erythroid cells

Cell Differentiation ◽

10.1016/0045-6039(72)90040-1 ◽

1972 ◽

Vol 1 (4) ◽

pp. 219-228 ◽

Cited By ~ 4

Author(s):

Antonio Fantoni ◽

Sandra Bordin ◽

Mario Lunadei

Keyword(s):

Ribosomal Rna ◽

Yolk Sac ◽

Erythroid Cells ◽

Rna Maturation

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Substitution of the Human β-Spectrin Promoter for the Human Aγ-Globin Promoter Prevents Silencing of a Linked Human β-Globin Gene in Transgenic Mice

Molecular and Cellular Biology ◽

10.1128/mcb.18.11.6634 ◽

1998 ◽

Vol 18 (11) ◽

pp. 6634-6640 ◽

Cited By ~ 30

Author(s):

Denise E. Sabatino ◽

Amanda P. Cline ◽

Patrick G. Gallagher ◽

Lisa J. Garrett ◽

George Stamatoyannopoulos ◽

...

Keyword(s):

Transgenic Mice ◽

Fetal Liver ◽

Globin Gene ◽

Gene Promoter ◽

Yolk Sac ◽

Globin Genes ◽

Erythroid Cells ◽

Globin Mrna ◽

Globin Promoter ◽

In Erythroid Cells

ABSTRACT During development, changes occur in both the sites of erythropoiesis and the globin genes expressed at each developmental stage. Previous work has shown that high-level expression of human β-like globin genes in transgenic mice requires the presence of the locus control region (LCR). Models of hemoglobin switching propose that the LCR and/or stage-specific elements interact with globin gene sequences to activate specific genes in erythroid cells. To test these models, we generated transgenic mice which contain the human Aγ-globin gene linked to a 576-bp fragment containing the human β-spectrin promoter. In these mice, the β-spectrin Aγ-globin (βsp/Aγ) transgene was expressed at high levels in erythroid cells throughout development. Transgenic mice containing a 40-kb cosmid construct with the micro-LCR, βsp/Aγ-, ψβ-, δ-, and β-globin genes showed no developmental switching and expressed both human γ- and β-globin mRNAs in erythroid cells throughout development. Mice containing control cosmids with the Aγ-globin gene promoter showed developmental switching and expressed Aγ-globin mRNA in yolk sac and fetal liver erythroid cells and β-globin mRNA in fetal liver and adult erythroid cells. Our results suggest that replacement of the γ-globin promoter with the β-spectrin promoter allows the expression of the β-globin gene. We conclude that the γ-globin promoter is necessary and sufficient to suppress the expression of the β-globin gene in yolk sac erythroid cells.

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Primitive and Definitive Erythropoiesis

Blood ◽

10.1182/blood.v120.21.sci-37.sci-37 ◽

2012 ◽

Vol 120 (21) ◽

pp. SCI-37-SCI-37

Author(s):

James Palis

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Yolk Sac ◽

Erythroid Cells ◽

Transient Wave ◽

Self Renewal ◽

Primitive Erythropoiesis ◽

Definitive Erythropoiesis

Abstract Abstract SCI-37 Studies in mammalian and nonmammalian vertebrate embryos indicate that erythropoiesis comes in two flavors: primitive and definitive. The primitive erythroid lineage in mammalian embryos is characterized by a transient wave of lineage-committed progenitors that emerge from the yolk sac and generate a wave of precursors that synchronously mature in the bloodstream. Primitive erythroid precursors dynamically regulate embryonic globin gene expression and ultimately enucleate to form erythrocytes. Primitive erythropoiesis is superseded by definitive erythroid cells that mature extravascularly in association with macrophage cells. Studies in the mouse embryo indicate that definitive erythropoiesis has two distinct developmental origins. The first is a transient wave of erythro-myeloid progenitors (EMP) that emerge from the yolk sac and seed the early fetal liver. The second is a long-term program of erythropoiesis derived from hematopoietic stem cells. Erythropoietin is the central regulator of definitive erythropoiesis, in part by regulating the survival of committed progenitors. In contrast, the role of erythropoietin in primitive erythropoiesis remains poorly understood. Recent studies indicate that erythropoietin does not regulate the primitive erythroid progenitor compartment, but rather plays a critical role in establishing an antiapoptotic state during the terminal maturation of primitive erythroblasts. EMP-derived proerythroblasts are capable of extensive self-renewal in vitro, while primitive erythroid progenitors are incapable of self-renewal under the same conditions. These studies, taken together, indicate that the primitive and definitive forms of erythropoiesis have fundamental differences in the regulation of red cell output. The overlapping emergence of primitive and definitive erythroid lineages in differentiating embryonic stem cells suggests that the transient yolk-sac-derived primitive and EMP-derived definitive erythroid programs are recapitulated in vitro. These studies offer the hope that human embryonic stem cells can serve as a source of functional definitive erythroid cells for transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

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Electronmicroscopic and biochemical observations on erythroid cells in congenital dyserythropoietic anemia type II

Virchows Archiv A Pathological Anatomy and Histology ◽

10.1007/bf00432200 ◽

1974 ◽

Vol 363 (1) ◽

pp. 1-15 ◽

Cited By ~ 4

Author(s):

Peter Kerkhoven ◽

Hans R. Marti ◽

George Hug

Keyword(s):

Type Ii ◽

Erythroid Cells ◽

Congenital Dyserythropoietic Anemia

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“Maturational” globin switching in primary primitive erythroid cells

Blood ◽

10.1182/blood-2005-08-3097 ◽

2006 ◽

Vol 107 (4) ◽

pp. 1665-1672 ◽

Cited By ~ 94

Author(s):

Paul D. Kingsley ◽

Jeffrey Malik ◽

Rachel L. Emerson ◽

Timothy P. Bushnell ◽

Kathleen E. McGrath ◽

...

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Expression Patterns ◽

Yolk Sac ◽

Transcriptional Level ◽

Globin Genes ◽

Erythroid Cells ◽

Transcript Levels ◽

Chromosomal Arrangement ◽

Sequential Appearance

Mammals have 2 distinct erythroid lineages. The primitive erythroid lineage originates in the yolk sac and generates a cohort of large erythroblasts that terminally differentiate in the bloodstream. The definitive erythroid lineage generates smaller enucleated erythrocytes that become the predominant cell in fetal and postnatal circulation. These lineages also have distinct globin expression patterns. Our studies in primary murine primitive erythroid cells indicate that βH1 is the predominant β-globin transcript in the early yolk sac. Thus, unlike the human, murine β-globin genes are not up-regulated in the order of their chromosomal arrangement. As primitive erythroblasts mature from proerythroblasts to reticulocytes, they undergo a βH1- to ϵy-globin switch, up-regulate adult β1- and β2-globins, and down-regulate ζ-globin. These changes in transcript levels correlate with changes in RNA polymerase II density at their promoters and transcribed regions. Furthermore, the ϵy- and βH1-globin genes in primitive erythroblasts reside within a single large hyperacetylated domain. These data suggest that this “maturational” βH1- to ϵy-globin switch is dynamically regulated at the transcriptional level. Globin switching during ontogeny is due not only to the sequential appearance of primitive and definitive lineages but also to changes in globin expression as primitive erythroblasts mature in the bloodstream.

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Human peptidylarginine deiminase type II: molecular cloning, gene organization, and expression in human skin

Archives of Biochemistry and Biophysics ◽

10.1016/s0003-9861(02)00516-7 ◽

2002 ◽

Vol 407 (1) ◽

pp. 25-31 ◽

Cited By ~ 72

Author(s):

Akihito Ishigami ◽

Takako Ohsawa ◽

Hiroaki Asaga ◽

Kyoichi Akiyama ◽

Masashi Kuramoto ◽

...

Keyword(s):

Molecular Cloning ◽

Human Skin ◽

Gene Organization ◽

Type Ii ◽

Peptidylarginine Deiminase

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Increased and type II-specific expression of peptidylarginine deiminase in activated microglia but not hyperplastic astrocytes following kainic acid-evoked neurodegeneration in the rat brain

Neuroscience Letters ◽

10.1016/s0304-3940(02)00334-8 ◽

2002 ◽

Vol 326 (2) ◽

pp. 129-132 ◽

Cited By ~ 39

Author(s):

Hiroaki Asaga ◽

Kyoichi Akiyama ◽

Takako Ohsawa ◽

Akihito Ishigami

Keyword(s):

Rat Brain ◽

Kainic Acid ◽

Type Ii ◽

Peptidylarginine Deiminase ◽

Specific Expression ◽

Activated Microglia

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Terminal stages of erythroid differentiation: persistent production of globin messenger RNA is necessary to sustain globin synthesis

Blood ◽

10.1182/blood.v52.1.171.bloodjournal521171 ◽

1978 ◽

Vol 52 (1) ◽

pp. 171-180

Author(s):

E Ullu ◽

MG Farace ◽

R Gambari ◽

P Orsi ◽

M Lunadei ◽

...

Keyword(s):

Messenger Rna ◽

Relative Proportion ◽

Terminal Differentiation ◽

Yolk Sac ◽

Globin Genes ◽

Erythroid Cells ◽

Globin Mrna ◽

Rna Molecules ◽

Cell Functions ◽

Globin Synthesis

The kinetic relationship between the globin mRNA accumulation and the rate of synthesis of globin chains was studied during the terminal stages of differentiation in erythroid cells derived from the yolk sac of mouse fetuses. RNA derived from the whole cells and from different cell compartments were hybridized to DNA complementary to embryonic globin mRNA. The relative proportion of embryonic globin RNA molecules and their absolute number per cell were estimated on the 11th, 12th, and 13th days of mouse fetal development. During erythroid terminal differentiation globin mRNA became progressively predominant on polyribosomes along with the progressive specialization of cell functions. The number of embryonic globin RNA molecules per cell remained constant while yolk sac erythroid cells underwent two rounds of cell division. These data indicate that the transcription of globin genes is operative throughout the last stages of terminal differentiation and that there is no detectable storage of globin RNA sequences in these cells. The rates of accumulation of mRNA molecules and of globin synthesis both seem correlated to the length of the cell cycle.

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