scholarly journals Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

2018 ◽  
Author(s):  
Jose A. Hernandez ◽  
Victoria L. Castro ◽  
Nayeli Reyes-Nava ◽  
Laura P. Montes ◽  
Anita M. Quintana
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Cholesterol Synthesis ◽  
Cell Development ◽  
Cholesterol Homeostasis ◽  
List Type ◽  
Key Points ◽  
Primitive Erythropoiesis ◽  
Gata1 Transcription Factor

AbstractErythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression ofGATA1are not completely characterized. Cholesterol is one potential upstream mediator ofGATA1expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in thehmgcs1gene (Vu57 allele).hmgcs1encodes the first enzyme in the cholesterol synthesis pathway and mutation ofhmgcs1inhibits cholesterol synthesis. We analyzed the number of RBCs inhmgcs1mutants and their wildtype siblings. Mutation ofhmgcs1resulted in a decrease in the number of mature RBCs, which coincides with reducedgata1aexpression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but thatgata1aexpression is isoprenoid dependent. Collectively, our results reveal two novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.Key PointsThe products of the cholesterol synthesis pathway regulate red blood cell development during primitive erythropoiesis.Isoprenoids regulate erythropoiesis by modulating the expression of the GATA1 transcription factor.

scholarly journals Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development

2019 ◽  
Vol 3 (8) ◽  
pp. 1244-1254 ◽  
Author(s):  
Jose A. Hernandez ◽  
Victoria L. Castro ◽  
Nayeli Reyes-Nava ◽  
Laura P. Montes ◽  
Anita M. Quintana
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Cholesterol Synthesis ◽  
Cholesterol Homeostasis ◽  
Wild Type ◽  
Primitive Erythropoiesis ◽  
Gata1 Transcription Factor ◽  
Upstream Regulators

Abstract Erythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is 1 potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wild-type siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal 2 novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.

scholarly journals Zebrafish etv7 regulates red blood cell development through the cholesterol synthesis pathway

2013 ◽  
Vol 7 (2) ◽  
pp. 265-270 ◽  
Author(s):  
A. M. Quintana ◽  
F. Picchione ◽  
R. I. Klein Geltink ◽  
M. R. Taylor ◽  
G. C. Grosveld
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cholesterol Synthesis ◽  
Cell Development

scholarly journals Widespread and dynamic translational control of red blood cell development

Blood ◽  
2017 ◽  
Vol 129 (5) ◽  
pp. 619-629 ◽  
Author(s):  
Juan R. Alvarez-Dominguez ◽  
Xu Zhang ◽  
Wenqian Hu
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Translational Control ◽  
Erythroid Differentiation ◽  
Cell Development ◽  
Key Points ◽  
Terminal Erythroid Differentiation

Key Points Critical roles for dynamic translational control during terminal erythroid differentiation. RBM38 can regulate translation during terminal erythropoiesis.

Pathophysiology of Thrombocytopenia and Anemia in Mice Lacking Transcription Factor NF-E2

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3037-3047 ◽  
Author(s):  
Jack Levin ◽  
Jin-Peng Peng ◽  
Georgiann R. Baker ◽  
Jean-Luc Villeval ◽  
Patrick Lecine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Fetal Life ◽  
Wild Type ◽  
Cell Lineages ◽  
Cell Fragments ◽  
Proliferation Potential

Abstract Expression of the p45 subunit of transcription factor NF-E2 is restricted to selected blood cell lineages, including megakaryocytes and developing erythrocytes. Mice lacking p45 NF-E2 show profound thrombocytopenia, resulting from a late arrest in megakaryocyte differentiation, and a number of red blood cell defects, including anisocytosis and hypochromia. Here we report results of studies aimed to explore the pathophysiology of these abnormalities. Mice lacking NF-E2 produce very few platelet-like particles that display highly disorganized ultrastructure and respond poorly to platelet agonists, features consistent with the usually lethal hemorrhage in these animals. Thrombocytopenia was evident during fetal life and was not corrected by splenectomy in adults. Surprisingly, fetal NF-E2–deficient megakaryocyte progenitors showed reduced proliferation potential in vitro. Thus, NF-E2 is required for regulated megakaryocyte growth as well as for differentiation into platelets. All the erythroid abnormalities were reproduced in lethally irradiated wild-type recipients of hematopoietic cells derived from NF-E2-null fetuses. Whole blood from mice lacking p45 NF-E2 showed numerous small red blood cell fragments; however, survival of intact erythrocytes in vivo was indistinguishable from control mice. Considered together, these observations indicate a requirement for NF-E2 in generating normal erythrocytes. Despite impressive splenomegaly at baseline, mice lacking p45 NF-E2 survived splenectomy, which resulted in increased reticulocyte numbers. This reveals considerable erythroid reserve within extra-splenic sites of hematopoiesis and suggests a role for the spleen in clearing abnormal erythrocytes. Our findings address distinct aspects of the requirements for NF-E2 in blood cell homeostasis and establish its roles in proper differentiation of megakaryocytes and erythrocytes.

scholarly journals Reduced red blood cell deformability in Plasmodium knowlesi malaria

2018 ◽  
Vol 2 (4) ◽  
pp. 433-443 ◽  
Author(s):  
Bridget E. Barber ◽  
Bruce Russell ◽  
Matthew J. Grigg ◽  
Rou Zhang ◽  
Timothy William ◽  
...  
Keyword(s):  
Blood Cell ◽  
Disease Severity ◽  
Red Blood Cell ◽  
Plasmodium Knowlesi ◽  
Cell Deformability ◽  
Red Blood Cell Deformability ◽  
Key Points

Key PointsRBC-D is reduced in humans with knowlesi malaria in proportion to disease severity. In humans, but not the macaque hosts, deformability of uRBCs is reduced and is related to the presence of echinocytes.

scholarly journals Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor

2017 ◽  
Vol 21 (6) ◽  
pp. 731-741.e10 ◽  
Author(s):  
Joana Mendonca Santos ◽  
Gabrielle Josling ◽  
Philipp Ross ◽  
Preeti Joshi ◽  
Lindsey Orchard ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Cell Invasion ◽  
Red Blood Cell ◽  
Malaria Parasite

Pathophysiology of Thrombocytopenia and Anemia in Mice Lacking Transcription Factor NF-E2

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3037-3047 ◽  
Author(s):  
Jack Levin ◽  
Jin-Peng Peng ◽  
Georgiann R. Baker ◽  
Jean-Luc Villeval ◽  
Patrick Lecine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Fetal Life ◽  
Wild Type ◽  
Cell Lineages ◽  
Cell Fragments ◽  
Proliferation Potential

Expression of the p45 subunit of transcription factor NF-E2 is restricted to selected blood cell lineages, including megakaryocytes and developing erythrocytes. Mice lacking p45 NF-E2 show profound thrombocytopenia, resulting from a late arrest in megakaryocyte differentiation, and a number of red blood cell defects, including anisocytosis and hypochromia. Here we report results of studies aimed to explore the pathophysiology of these abnormalities. Mice lacking NF-E2 produce very few platelet-like particles that display highly disorganized ultrastructure and respond poorly to platelet agonists, features consistent with the usually lethal hemorrhage in these animals. Thrombocytopenia was evident during fetal life and was not corrected by splenectomy in adults. Surprisingly, fetal NF-E2–deficient megakaryocyte progenitors showed reduced proliferation potential in vitro. Thus, NF-E2 is required for regulated megakaryocyte growth as well as for differentiation into platelets. All the erythroid abnormalities were reproduced in lethally irradiated wild-type recipients of hematopoietic cells derived from NF-E2-null fetuses. Whole blood from mice lacking p45 NF-E2 showed numerous small red blood cell fragments; however, survival of intact erythrocytes in vivo was indistinguishable from control mice. Considered together, these observations indicate a requirement for NF-E2 in generating normal erythrocytes. Despite impressive splenomegaly at baseline, mice lacking p45 NF-E2 survived splenectomy, which resulted in increased reticulocyte numbers. This reveals considerable erythroid reserve within extra-splenic sites of hematopoiesis and suggests a role for the spleen in clearing abnormal erythrocytes. Our findings address distinct aspects of the requirements for NF-E2 in blood cell homeostasis and establish its roles in proper differentiation of megakaryocytes and erythrocytes.

scholarly journals Csk-binding protein controls red blood cell development via regulation of Lyn tyrosine kinase activity

2017 ◽  
Vol 46 ◽  
pp. 70-82.e10
Author(s):  
Janice H.C. Plani-Lam ◽  
Neli S. Slavova-Azmanova ◽  
Nicole Kucera ◽  
Alison Louw ◽  
Jiulia Satiaputra ◽  
...  
Keyword(s):  
Blood Cell ◽  
Tyrosine Kinase ◽  
Red Blood Cell ◽  
Kinase Activity ◽  
Binding Protein ◽  
Cell Development ◽  
Tyrosine Kinase Activity ◽  
Lyn Tyrosine Kinase

scholarly journals The role of Friend of GATA in primitive red blood cell development

2009 ◽  
Vol 331 (2) ◽  
pp. 527
Author(s):  
Mizuho S. Mimoto ◽  
Jan L. Christian
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Development
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