Erythropoiesis: Development and Differentiation

Dzierzak, Elaine; Philipsen, Sjaak

doi:10.1101/cshperspect.a011601

Cited by 290 publications

(316 citation statements)

References 121 publications

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“…Variation in many phenotypic features, such as metabolic properties, decrease in cell size, increases in hemoglobinization, alterations in membrane characteristics, epigenetic and nuclear changes with chromatin condensation, and, ultimately, enucleation, have led to the conclusion that terminal erythroid differentiation is a unique process, with each cell division simultaneously coupled with differentiation. 2,7,8,14 In contrast to most cell types, in which each cell division generates 2 daughter cells that are nearly identical to the mother cell, during terminal erythroid differentiation, the 2 daughter cells are structurally and functionally different than the mother cell from which they are derived. This conclusion has been supported on a limited basis by gene expression analyses of varying populations of murine and human erythroid cells.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In the mammalian embryo and fetus, erythroid cells have differing developmental origins, with the primitive erythroid cell lineage developing from yolk sac-derived erythroid progenitors, and the definitive cell lineage maturing from 2 different developmentally regulated stem and progenitor cell populations. [3][4][5][6] These cells have different programs of regulation, with variation in spatial, temporal, and site-specific differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…Traditionally, erythropoiesis has been divided into 3 stages: early erythropoiesis, terminal erythroid differentiation, and reticulocyte maturation. 2 Early erythropoiesis involves commitment of multi-lineage progenitors into erythroid progenitor cells, with proliferation and differentiation into erythroid burst-forming unit cells, followed by erythroid colonyforming unit cells, then differentiation into proerythroblasts. Terminal erythroid differentiation begins with proerythroblasts differentiating into basophilic, then polychromatic, then orthochromatic erythroblasts that enucleate to become reticulocytes.…”

Section: Introductionmentioning

confidence: 99%

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Global transcriptome analyses of human and murine terminal erythroid differentiation

Schulz

et al. 2014

Blood

311

340

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• Transcriptome analyses of human and murine reveal significant stage and speciesspecific differences across stages of terminal erythroid differentiation.• These transcriptomes provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis.We recently developed fluorescence-activated cell sorting (FACS)-based methods to purify morphologically and functionally discrete populations of cells, each representing specific stages of terminal erythroid differentiation. We used these techniques to obtain pure populations of both human and murine erythroblasts at distinct developmental stages. RNA was prepared from these cells and subjected to RNA sequencing analyses, creating unbiased, stage-specific transcriptomes. Tight clustering of transcriptomes from differing stages, even between biologically different replicates, validated the utility of the FACSbased assays. Bioinformatic analyses revealed that there were marked differences between differentiation stages, with both shared and dissimilar gene expression profiles defining each stage within transcriptional space. There were vast temporal changes in gene expression across the differentiation stages, with each stage exhibiting unique transcriptomes. Clustering and network analyses revealed that varying stage-specific patterns of expression observed across differentiation were enriched for genes of differing function. Numerous differences were present between human and murine transcriptomes, with significant variation in the global patterns of gene expression. These data provide a significant resource for studies of normal and perturbed erythropoiesis, allowing a deeper understanding of mechanisms of erythroid development in various inherited and acquired erythroid disorders. (Blood. 2014;123(22):3466-3477) IntroductionMammalian erythropoiesis is an excellent example of the complex changes in temporal, developmental, and differentiation stage-specific gene expression exhibited by a single cell type.1,2 In the mammalian embryo and fetus, erythroid cells have differing developmental origins, with the primitive erythroid cell lineage developing from yolk sac-derived erythroid progenitors, and the definitive cell lineage maturing from 2 different developmentally regulated stem and progenitor cell populations. [3][4][5][6] These cells have different programs of regulation, with variation in spatial, temporal, and site-specific differentiation.In the adult, mature erythrocytes are the terminally differentiated final cellular product derived from hematopoietic stem and progenitor cells (HSPC). HSPCs undergo a series of lineage choice fate decisions, with increasingly restricted potential, ultimately committing to the erythroid lineage and beginning erythropoiesis. Traditionally, erythropoiesis has been divided into 3 stages: early erythropoiesis, terminal erythroid differentiation, and reticulocyte maturation.2 Early erythropoiesis involves commitment of multi-lineage progenitors into erythroid progenitor cells, with proliferation and d...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Global transcriptome analyses of human and murine terminal erythroid differentiation

Schulz

et al. 2014

Blood

311

340

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“…31,32 Complex transcription and splicing programs drive this process. 11,25,27,28 We therefore determined whether an IR program exists during terminal maturation.…”

Section: Ir During Murine Terminal Erythroid Maturationmentioning

confidence: 99%

“…These results are notable because erythropoiesis involves producing optimal heme levels, metabolizing iron, controlling the number of cell divisions, globally changing mRNA levels, mass-producing erythroid proteins, and remodeling the cell membrane and cytoskeletal scaffold. 31,32 In summary, dynamic IR genes are enriched for biologically important GO terms and KEGG pathways during murine and human erythroid maturation.…”

Section: Enrichment Of Go Terms and Kegg Pathways Among Differentialmentioning

confidence: 99%

A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages

Edwards

Ritchie

Wong³

et al. 2016

Blood

100

108

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• Dynamic intron retention programs exist in the murine megakaryocyte and erythroid and human erythroid lineages.• Intron retention inversely correlates with expression levels of a large set of transcripts.Intron retention (IR) is a form of alternative splicing that can affect mRNA levels through nonsense-mediated decay or by nuclear mRNA detention. A complex, dynamic IR pattern has been described in maturing mammalian granulocytes, but it is unknown whether IR occurs broadly in other hematopoietic lineages. We globally assessed IR in primary maturing mammalian erythroid and megakaryocyte (MK) lineages as well as their common progenitor cells (MEPs). Both lineages exhibit an extensive differential IR program involving hundreds of introns and genes with an overwhelming loss of IR in erythroid cells and MKs compared with MEPs. Moreover, complex IR patterns were seen throughout murine erythroid maturation. Similarly complex patterns were observed in human erythroid differentiation, but not involving the murine orthologous introns or genes. Despite the common origin of erythroid cells and MKs, and overlapping gene expression patterns, the MK IR program is entirely distinct from that of the erythroid lineage with regards to introns, genes, and affected gene ontologies. Importantly, our results suggest that IR serves to broadly regulate mRNA levels. These findings highlight the importance of this understudied form of alternative splicing in gene regulation and provide a useful resource for studies on gene expression in the MK and erythroid lineages. (Blood. 2016;127(17):e24-e34)

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A life‐time of hematopoietic cell function: ascent, stability, and decline

Popravko,

Mackintosh,

Dzierzak

2024

FEBS Letters

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Aging is a set of complex processes that occur temporally and continuously. It is generally a unidirectional progression of cellular and molecular changes occurring during the life stages of cells, tissues and ultimately the whole organism. In vertebrate organisms, this begins at conception from the first steps in blastocyst formation, gastrulation, germ layer differentiation, and organogenesis to a continuum of embryonic, fetal, adolescent, adult, and geriatric stages. Tales of the “fountain of youth” and songs of being “forever young” are dominant ideas informing us that growing old is something science should strive to counteract. Here, we discuss the normal life stages of the blood system, particularly the historical recognition of its importance in the early growth stages of vertebrates, and what this means with respect to progressive gain and loss of hematopoietic function in the adult.

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Erythropoiesis: Development and Differentiation

Cited by 290 publications

References 121 publications

Global transcriptome analyses of human and murine terminal erythroid differentiation

Global transcriptome analyses of human and murine terminal erythroid differentiation

A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages

A life‐time of hematopoietic cell function: ascent, stability, and decline

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