Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal and disordered erythropoiesis in vivo

Hu, Jingping; Liu, Jing; Xue, Fumin; Halverson, Gregory R.; Reid, Marion E.; Guo, Anqi; Chen, Lixiang; Raza, Azra; Galili, Naomi; Jaffray, Julie; Lane, Joseph M.; Chasis, Joel Anne; Taylor, Naomi; Mohandas, Narla; An, Xiuli

doi:10.1182/blood-2013-01-476390

Cited by 328 publications

(410 citation statements)

References 36 publications

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“…Despite the technical limitations that we have highlighted, including probeset differences and variation in sample preparation, we consistently found substantial divergence of the transcriptional landscape of erythropoiesis between humans and mice using numerous cross-comparisons. Future cross-species comparative studies can be greatly fine-tuned by using improved purification methods and distinct phenotypic markers to obtain highly purified human and mouse erythroblasts at distinct stages, similar to methods recently reported (12). In addition, the use of RNA sequencing data may help eliminate some issues arising from microarray probeset differences that were faced in this analysis.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional divergence and conservation of human and mouse erythropoiesis

Pishesha

Thiru

Shi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Mouse models have been instrumental in advancing our understanding of blood cell production. Although many studies have suggested specific differences between human and mouse red cell production (erythropoiesis), a global study of such similarities and differences has been lacking. By computationally comparing global gene expression data from adult human and mouse erythroid precursors representing the distinct stages of maturation, we showed that, while the overall transcriptional landscape has changed, critical erythroid gene signatures and transcriptional regulators have remained conserved. Importantly, these analyses can serve as a tool to integrate data between human and mouse erythropoiesis research, explain why certain human blood diseases are not faithfully recapitulated in mouse models, and highlight hurdles in translating therapeutic findings from mice to humans.

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Section: Discussionmentioning

confidence: 99%

“…The earliest committed erythroid progenitor is the burstforming unit erythroid (BFU-E) (12,13). BFU-Es undergo limited self-renewal divisions and differentiate to the colonyforming unit erythroid (CFU-E) (14).…”

mentioning

confidence: 99%

Transcriptional divergence and conservation of human and mouse erythropoiesis

Pishesha

Thiru

Shi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…44,45 In order to maximize the specificity of the information afforded by these techniques, it is essential to start with well-defined populations. A recent report pro- vided an excellent protocol to identify populations at distinct stages of erythroid differentiation, 46 but early erythroid culture has proved more challenging.…”

Section: Discussionmentioning

confidence: 99%

“…The standard deviation found within the experimental data was 222. 44 Table 2 shows the rates (divisions per hour) and delays (hours) obtained from the optimization algorithm. The model was validated using a second, independent experimental data set (dataset B) in two different ways (Online Supplementary Methods and Online Supplementary Figure S5), and indicated high confidence in the model and parameter values.…”

Section: A B Cmentioning

confidence: 99%

Mathematical modeling reveals differential effects of erythropoietin on proliferation and lineage commitment of human hematopoietic progenitors in early erythroid culture

et al. 2015

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“…The earliest committed erythroid progenitor is the burst-forming unit erythroid, which differentiates to produce CFU-erythroid (7). Terminal erythropoiesis begins at this stage and involves as many as six terminal divisions, differential regulation of erythroid-specific genes, nuclear changes, and extrusion of mitochondria (all species) and the nucleus (mammals) (6).…”

mentioning

confidence: 99%

Inactivation of 3- hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy

Davuluri

Song

Liu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are the site of iron utilization, wherein imported iron is incorporated into heme or iron-sulfur clusters. Previously, we showed that a cytosolic siderophore, which resembles a bacterial siderophore, facilitates mitochondrial iron import in eukaryotes, including zebrafish. An evolutionarily conserved 3-hydroxy butyrate dehydrogenase, 3-hydroxy butyrate dehydrogenase 2 (Bdh2), catalyzes a rate-limiting step in the biogenesis of the eukaryotic siderophore. We found that inactivation of bdh2 in developing zebrafish embryo results in heme deficiency and delays erythroid maturation. The basis for this erythroid maturation defect is not known. Here we show that bdh2 inactivation results in mitochondrial dysfunction and triggers their degradation by mitophagy. Thus, mitochondria are prematurely lost in bdh2-inactivated erythrocytes. Interestingly, bdh2-inactivated erythroid cells also exhibit genomic alterations as indicated by transcriptome analysis. Reestablishment of bdh2 restores mitochondrial function, prevents premature mitochondrial degradation, promotes erythroid development, and reverses altered gene expression. Thus, mitochondrial communication with the nucleus is critical for erythroid development. T he zebrafish (Danio rerio) is a well-established model system to study vertebrate hematopoiesis: zebrafish hematopoiesis is strikingly similar to mammalian hematopoiesis, and zebrafish have inherent experimental advantages (1). In the zebrafish embryo, hematopoiesis occurs in spatially distinct steps: the primitive or first wave of hematopoiesis occurs in two distinct anatomical locations, the posterior lateral mesoderm, which forms the intermediate cell mass (ICM) and is the site of erythroid development, and the anterior lateral mesoderm, which is the site of myeloid development. The definitive or second wave of hematopoiesis arises from self-renewing hematopoietic stem cells located in the wall of dorsal aorta (2, 3). These two waves of hematopoiesis are tightly controlled at the transcriptional level (4, 5).In erythropoiesis, pluripotent hematopoietic stem cells give rise to committed erythroid progenitor cells and to additional progenitors and precursors (6). The earliest committed erythroid progenitor is the burst-forming unit erythroid, which differentiates to produce CFU-erythroid (7). Terminal erythropoiesis begins at this stage and involves as many as six terminal divisions, differential regulation of erythroid-specific genes, nuclear changes, and extrusion of mitochondria (all species) and the nucleus (mammals) (6). Terminal erythropoiesis involves predominantly three cell types: proerythroblasts, basophilic erythroblasts, and polychromatophilic erythroblasts, which undergo morphologically distinguishable pattern of differentiation (8). In terminal erythropoiesis, polychromatophilic/orthochromatophilic erythroblasts give rise to reticulocytes. Reticulocytes lose all of their organelles, including mitochondria (8). The primary method used to eliminate mitochondria is mitophagy, a form of ...

show abstract

Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal and disordered erythropoiesis in vivo

Cited by 328 publications

References 36 publications

Transcriptional divergence and conservation of human and mouse erythropoiesis

Transcriptional divergence and conservation of human and mouse erythropoiesis

Mathematical modeling reveals differential effects of erythropoietin on proliferation and lineage commitment of human hematopoietic progenitors in early erythroid culture

Inactivation of 3- hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy

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