Distinct Waves from the Hemogenic Endothelium Give Rise to Layered Lymphoid Tissue Inducer Cell Ontogeny

Simic, Milesa; Manosalva, Iris; Spinelli, Lionel; Gentek, Rebecca; Shayan, Raheleh R.; Siret, Carole; Girard-Madoux, Mathilde J.H.; Wang, Shuaiwei; Fabritus, Lauriane de; Verschoor, Janneke; Kerdiles, Yann M.; Bajénoff, Marc; Stumm, Ralf; Golub, Rachel; Pavert, Serge A. van de

doi:10.1016/j.celrep.2020.108004

Cited by 36 publications

(86 citation statements)

References 44 publications

(75 reference statements)

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“…A critical advantage of this system compared to the Csf1r MeriCreMer Rosa26 YFP approach is that it bypasses lineage bias that may occur due to role of Csf1r in myeloid cells. By taking advantage of spatiotemporal differences in the generation of EMP and HSC from endothelia (Gentek et al, 2018; Simic et al, 2020), HSC were selectively labeled by injection of 4-hydroxytamoxifen (OHT) at E10.5, whereas EMP were labeled by injection of OHT at E7.5 with the caveat that this also labeled some precursors of HSC-generating endothelium ( Figure S1A-B ). To control for inherent variabilities between individual pulse chase labeling manipulations and to take into account the labeling of HSC by both injection timepoints, the percentage of YFP among mature cells was normalized either to the percentage of YFP among microglia (MG, CD45 + Kit neg F4/80 hi CD11b + ) for E7.5 OHT or to the percentage of YFP among LSK (Lin neg Sca1 + Kit + ) for E10.5 OHT ( Figure 1A-B ).…”

Section: Resultsmentioning

confidence: 99%

“…HSC are defined by the ability for long-term multilineage reconstitution when transplanted to adults. Adding to the complexity of these overlapping waves are developmentally restricted HSC that specialize in tissue resident lymphoid output (Beaudin et al, 2016; Elsaid et al, 2020; Simic et al, 2020). Therefore there exist cells that are functionally important in adults but which are only produced during development.…”

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%

“…Pulse chase labeling has proven indispensable for tracing EMP independently of HSC using Csf1r MeriCreMer mice (Gomez Perdiguero et al, 2015; Schulz et al, 2012). Recently, Cdh5 CreERT2 mice have been used to label EMP or HSC by separating the timing of labeling to encompass endothelial cells that give rise to hemogenic endothelia at different stages (Gentek et al, 2018; Simic et al, 2020).…”

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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Freyer

Iturri

Biton

et al. 2020

Preprint

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“…LTi-like ILC3s identified in these adult lymphoid tissues may contribute to their repair, thus indirectly enhancing the recovery of efficient antigen-specific immune response and reducing the risks of opportunistic infection and relapse. Although it is very difficult to study these LTi-like ILC3s in humans, recent findings in mice showed that embryonic LTi cells are replaced in adult lymphoid tissues by HSC-derived cells (74). Since LTi cells in mice have a specific role in the restoration of spleen integrity after infection (75), it is possible that LTi-like ILC3s deriving from HSCs may contribute to lymphoid tissue regeneration upon transplantation.…”

Section: Future Directionsmentioning

confidence: 99%

Helper Innate Lymphoid Cells in Allogenic Hematopoietic Stem Cell Transplantation and Graft Versus Host Disease

et al. 2020

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Helper Innate Lymphoid Cells (hILCs), including ILC1s, ILC2s, and ILC3s, are mainly localized at the mucosal barriers where they play an important role in tissue regeneration and homeostasis through the secretion of specific sets of cytokines. The recent identification of a circulating ILC precursor able to generate all ILC mature subsets in physiological conditions, suggests that "ILC-poiesis" may be important in the context of hematopoietic stem cell transplantation (HSCT). Indeed, in HSCT the conditioning regimen (chemotherapy and radiotherapy) and Graft vs Host Disease (GvHD) may cause severe damages to mucosal tissues. Therefore, it is conceivable that rapid reconstitution of the hILC compartment may be beneficial in HSCT, by promoting mucosal tissue repair/regeneration and providing protection from opportunistic infections. In this review, we will summarize the evidence for a role of hILCs in allogenic HSCT for the treatment of hematological malignancies in all its steps, from the preparative regimen to the immune reconstitution in the recipient. The protective properties of hILCs at the mucosal barrier interfaces make them an attractive target to exploit in future cellular therapies aimed at improving allogenic HSCT outcome.

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Fate-Mapping Macrophages: From Ontogeny to Functions

Ahlback,

Gentek

2023

Methods in Molecular Biology

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Distinct Waves from the Hemogenic Endothelium Give Rise to Layered Lymphoid Tissue Inducer Cell Ontogeny

Cited by 36 publications

References 44 publications

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

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

Helper Innate Lymphoid Cells in Allogenic Hematopoietic Stem Cell Transplantation and Graft Versus Host Disease

Fate-Mapping Macrophages: From Ontogeny to Functions

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