Yolk sac erythromyeloid progenitors sustain erythropoiesis throughout embryonic life

Soares-da-Silva, Francisca; Burlen-Defranoux, Odile; Elsaid, Ramy; Iturri, Lorea; Freyer, Laina; Sismeiro, Odile; Pinto-do-Ó, Perpétua; Perdiguero, Elisa Gomez; Cumano, Ana

doi:10.1101/2020.02.27.968230

Cited by 5 publications

(8 citation statements)

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“…These progenitors generate the first definitive erythrocytes, megakaryocytes, macrophages and other myeloid lineages such as neutrophils, granulocytes and mast cells, but lack HSC activity ( Palis et al, 1999 ; McGrath et al, 2015 ). Although EMPs are a transient population at early stages of embryonic development, they generate different tissue-resident macrophages that, depending on the organ, can persist throughout adulthood ( Gomez-Perdiguero et al, 2015 ), mast cells that are maintained until birth ( Gentek et al, 2018 ), and are the major producers of erythrocytes throughout embryonic life ( Soares-da-Silva et al, 2020 , Preprint).…”

Section: The Emergence Of the Hematopoietic System During Embryogenesmentioning

confidence: 99%

“…Hematopoietic progenitors (defined by c-Kit expression) are found in close association with DLK1 + hepatoblasts at E14.5 ( Sugiyama et al, 2013 ). Nevertheless, c-Kit + cells could mostly represent erythroid progenitors as they are the most frequent population at this stage ( Soares-da-Silva et al, 2020 , Preprint). Other approaches include the use of transgenic Ly6a-GFP (labeling Sca1 + cells) mice, that together with Runx1 localized HSPCs at E11.5 in close contact with endothelial cells ( Tamplin et al, 2015 ).…”

Section: The Colonization Of the Fl By The Hematopoietic Systemmentioning

confidence: 99%

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Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development

Soares-da-Silva

Peixoto

Cumano

et al. 2020

Front. Cell Dev. Biol.

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Hematopoietic stem cells (HSCs) generated during embryonic development are able to maintain hematopoiesis for the lifetime, producing all mature blood lineages. HSC transplantation is a widely used cell therapy intervention in the treatment of hematologic, autoimmune and genetic disorders. Its use, however, is hampered by the inability to expand HSCs ex vivo, urging for a better understanding of the mechanisms regulating their physiological expansion. In the adult, HSCs reside in the bone marrow, in specific microenvironments that support stem cell maintenance and differentiation. Conversely, while developing, HSCs are transiently present in the fetal liver, the major hematopoietic site in the embryo, where they expand. Deeper insights on the dynamics of fetal liver composition along development, and on how these different cell types impact hematopoiesis, are needed. Both, the hematopoietic and hepatic fetal systems have been extensively studied, albeit independently. This review aims to explore their concurrent establishment and evaluate to what degree they may cross modulate their respective development. As insights on the molecular networks that govern physiological HSC expansion accumulate, it is foreseeable that strategies to enhance HSC proliferation will be improved.

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Section: The Emergence Of the Hematopoietic System During Embryogenesmentioning

confidence: 99%

Section: The Colonization Of the Fl By The Hematopoietic Systemmentioning

confidence: 99%

Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development

Soares-da-Silva

Peixoto

Cumano

et al. 2020

Front. Cell Dev. Biol.

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“…EMP are generated from the blood island and vascular plexus of the extraembryonic yolk sac between embryonic days E8.25 and E11.5 (Frame, 2015; Kasaai et al, 2017; Lux et al, 2008; Palis et al, 1999). They are responsible for red blood cells that support embryonic survival until birth (Chen et al, 2011; Soares-da-Silva et al, 2021) and tissue resident macrophages and mast cells that persist into adult life and replenish independently of HSC (Ajami et al, 2011; Gentek et al, 2018; Ginhoux et al, 2010; Gomez Perdiguero et al, 2015; Hashimoto et al, 2013; Hoeffel et al, 2015; Schulz et al, 2012; Yona et al, 2013, 2013). Overlapping with EMP production is the wave of HSC that emerge intraembryonically (Ana Cumano et al, 1996; Cumano et al, 2001; Medvinsky and Dzierzak, 1996; Yvernogeau and Robin, 2017) from the aorta-gonad-mesonephros (AGM) region and other hemogenic sites (placenta, vitelline and umbilical arteries) between embryonic days E10 and E12 (De Bruijn et al, 2000; Gekas et al, 2005; Ottersbach and Dzierzak, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…The EMP origin of tissue resident macrophages and mast cells has been described (Gentek et al, 2018; Gomez Perdiguero et al, 2015; Hoeffel et al, 2015; Schulz et al, 2012), but the extent to which EMP and fetal HSC contribute to other mature hematopoietic cells during development and postnatal life has only recently begun to be revealed for erythroid and lymphoid lineages (Elsaid et al, 2021; Simic et al, 2020; Soares-da-Silva et al, 2021). Among myeloid cells, it is known that EMP are efficient at generating macrophages and megakaryocytes by direct differentiation within their niche of origin, the yolk sac (McGrath et al, 2015; Iturri et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…The fetal liver provides a stromal microenvironment important for both structural support as well as a trophic secretion of growth factors utilized in HSPC expansion and commitment (Gao et al, 2018). EMP are highly sensitized to erythropoietin compared to HSC (Soares-da-Silva et al, 2021), indicating that a competition for limiting growth factors within the fetal liver niche may act as a driving force for differentiation. Whether the same holds true for myeloid progenitors remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Overlapping Definitive Progenitor Waves Divide and Conquer to Build a Layered Hematopoietic System

Freyer

Iturri

Biton

et al. 2020

Preprint

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Adult innate immune cells are part of a layered hematopoietic system constructed from definitive hematopoietic stem and progenitor cells (HSPC) with diverse origins during development. One source of HSPC are fetal hematopoietic stem cells (HSC) that provide long-term reconstitution throughout life. However, the extent to which HSC produce mature cells in utero is only recently being uncovered. This is in part due to the added complexity of an overlapping wave of definitive progenitors that derive from yolk sac erythro-myeloid progenitors (EMP). HSC and EMP are generated from spatiotemporally distinct hemogenic endothelia, yet they both migrate to the fetal liver niche where they co-habitate and are presumed to reach their full potential. Delineation of the respective HSC and EMP pathways towards developmental immune cell differentiation has been confounded by challenges in ontogeny-specific cell labeling. In this study, in vivo inducible pulse chase labeling revealed that HSC contribute little to fetal myelopoiesis and that EMP are the predominant source of mature myeloid cells until birth. This is similar to what has been reported for the erythroid branch of hematopoiesis thereby establishing a developmentally-restricted privilege for erythro-myeloid differentiation from EMP compared to HSC. Tracing the origins of mature cells to the progenitor level by immunophenotyping and single cell RNA sequencing uncovered a dichotomy in the allocation of fetal liver EMP and HSC to myeloid progenitor subsets, both in timing and lineage bias. This has exposed an uncoupling between developmental granulopoiesis and monopoiesis from EMP and HSC pathways, and provides a framework for future studies of HSC-dependent and -independent hematopoiesis.HIGHLIGHTSEMP-to-HSC switch in fetal liver myelopoiesis occurs late in gestationEMP are efficient at producing early transit amplifying erythroid and myeloid intermediatesscRNA-seq reveals three trajectories of EMP myelopoiesisMyeloid lineage commitment during development is cell type and ontogeny specific

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Definitive Hematopoietic Stem Cells Minimally Contribute to Embryonic Hematopoiesis

Ulloa

Habbsa

Potts

et al. 2021

Preprint

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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 defined gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a new lineage tracing approach, we selectively tracked HSC output in situ and discovered significantly delayed lymphomyeloid contribution. Using a novel inducible HSC injury model, we demonstrated 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 the differences among embryonic HSC and progenitor populations will guide improved de novo generation and expansion of functional HSCs.

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Yolk sac erythromyeloid progenitors sustain erythropoiesis throughout embryonic life

Abstract: 33 34

Cited by 5 publications

References 54 publications

Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development

Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development

Overlapping Definitive Progenitor Waves Divide and Conquer to Build a Layered Hematopoietic System

Definitive Hematopoietic Stem Cells Minimally Contribute to Embryonic Hematopoiesis

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