Splitting of circulating red blood cells as<i>in vivo</i>-mechanism of erythrocyte maturation in developing zebrafish, chick and mouse embryos

Brönnimann, Daniel; Annese, Tiziana; Gorr, Thomas A.; Djonov, Valentin

doi:10.1242/jeb.184564

Cited by 9 publications

(4 citation statements)

References 29 publications

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“…We also analyzed erythroid cellular morphology in Giemsa stained erythroid cells. Consistent with the literature, as zebrafish erythroid cells mature, they elongate and become more elliptical (23-25) (Figure 1C). These data show that our FACS sorting method of isolating erythroid cells robustly recapitulates what was observed from previous methods of zebrafish erythroid cell isolation.…”

Section: Resultssupporting

confidence: 90%

Mitochondrial iron transport via MFRN1 is required for erythroid cell cycle progression

Chen

Danoff

West

et al. 2022

Preprint

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Erythroid cells are the main driver of iron utilization in vertebrates, as their main role is to synthesize hemoglobin to oxygenate the body's tissues. As such, iron is a key nutrient for the development and function of erythroid cells. When iron deficient, erythroid cells are both lacking in hemoglobin and exhibit differentiation defects. Currently, the efficacy of iron supplementation is monitored by measuring indices of erythroid hemoglobinization. However, its effect on erythroid differentiation is less clear. In this study, we used zebrafish with genetic iron metabolism defects to determine if iron supplementation could rescue erythropoietic defects in organisms that are iron deficient at the cellular and systemic level. To carry out this study, we developed a technique to sort Tg(globin lcr:EGFP) erythrocytes from single zebrafish embryos onto slides for imaging. We found that iron supplementation in mfrn1 mutant zebrafish, which carry a defect in mitochondrial iron trafficking, restored hemoglobinization but not erythroid cell number or terminal differentiation. Iron supplementation in fpn1 mutant zebrafish, which have defects in export of iron from yolk syncytial cells and intestinal epithelium, functioning a model of dietary iron deficiency, restored erythroid cell number but not terminal differentiation deficiencies. Our data suggests that in addition to adequate iron levels, correct regulation of iron trafficking is required for optimal erythroid iron utilization and terminal erythropoiesis.

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Section: Resultssupporting

confidence: 90%

Mitochondrial iron transport via MFRN1 is required for erythroid cell cycle progression

Chen

Danoff

West

et al. 2022

Preprint

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“…During vertebrate development, distinct hematopoietic cell types reside in particular anatomical locations at specific time points ( Stachura and Traver, 2016 ). For example, erythrocytes and thrombocytes travel rapidly in circulation ( Brönnimann et al, 2018 Khandekar et al, 2012 ); macrophages and dendritic cells can reside in the skin ( Zhan et al., 2018 ); neutrophils ubiquitously spread throughout circulation, epidermis, or congregating in stressed tissue ( Le Guyader et al, 2008 ); and T cells are abundant in the thymus ( Tian et al, 2017 ). To measure Prog+ and HSC contribution to T lymphocytes, we imaged mCherry fluorescence in the thymus in 5–16 dpf larvae ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis

et al. 2021

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Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single-cell transcriptomics, we define gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a lineage-tracing approach to selectively track HSC output in situ, we find significantly delayed lymphomyeloid contribution. An inducible HSC injury model demonstrates a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage, as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding these differences could improve de novo generation and expansion of functional HSCs.

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“…This enrichment is eliminated when embryos are treated with the CDK4/6 inhibitor palbociclib, leading to a significant increase of cells in the tailbud with low CDK activity (0.58±0.3), similar in range to the G1/G0 values we measured during time-lapse (0.69±0.17; Figure 7C-D). We also made the surprising observation that primitive red blood cells in the intermediate cell mass of 24 hours post-fertilization (hpf) embryos, which are nucleated in zebrafish, display high CDK activity (3.00±0.97) indicating that they are likely in the G2 phase of the cell cycle ( Figure 7-figure supplement 1E, 1F), suggesting that cell cycle regulation may be important for hematopoiesis (Bronnimann et al, 2018;De La Garza et al, 2019).…”

Section: Generation Of Inducible Cdk Sensor Transgenic Lines In Zebramentioning

confidence: 93%

Visualizing the metazoan proliferation-quiescence decision in vivo

Adikes

Kohrman

Martinez

et al. 2020

eLife

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Cell proliferation and quiescence are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these key events of the cell cycle in Caenorhabditis elegans and zebrafish through live-cell imaging. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from quiescent cells in G0, revealing a possible commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. Finally, we derive a predictive model of future proliferation behavior in C. elegans based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell-cycle control in a wide-range of developmental contexts.

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Splitting of circulating red blood cells asin vivo-mechanism of erythrocyte maturation in developing zebrafish, chick and mouse embryos

Cited by 9 publications

References 29 publications

Mitochondrial iron transport via MFRN1 is required for erythroid cell cycle progression

Mitochondrial iron transport via MFRN1 is required for erythroid cell cycle progression

Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis

Visualizing the metazoan proliferation-quiescence decision in vivo

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