Adult-repopulating lymphoid potential of yolk sac blood vessels is not confined to arterial endothelial cells

Wang, Chaojie; Gong, Yandong; Wei, Anbang; Huang, Tao; Hou, Siyuan; Du, Junjie; Li, Zongcheng; Wang, Junliang; Liu, Bing; Lan, Yu

doi:10.1007/s11427-021-1935-2

Cited by 8 publications

(5 citation statements)

References 84 publications

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“…No abnormal gross phenotype was observed in cKO embryos at E10.5–E11.0 (37–43 somite pairs) (Figure 1B). Notably, in the colony‐forming unit in culture (CFU‐C) assay, significantly increased total CFU‐C numbers were observed in the cKO AGM regions (Figure 1C), while no difference was detected in the yolk sac regions, which mainly due to rarely expression of Nupr1 in yolk sac cells [ 30 ] (Figure S1B,C, Supporting Information). Next, we performed transplantation experiments to evaluate the ability to generate adult repopulating HSCs in the AGM region with one embryo equivalent of E11.5 AGM cells transplanted into lethally irradiated adult recipient mice.…”

Section: Resultsmentioning

confidence: 99%

Nupr1 Negatively Regulates Endothelial to Hematopoietic Transition in the Aorta‐Gonad‐Mesonephros Region

et al. 2023

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In the aorta of mid-gestational mouse embryos, a specialized endothelial subpopulation termed hemogenic endothelial cells (HECs) develops into hematopoietic stem and progenitor cells (HSPCs), through a conserved process of endothelial-to-hematopoietic transition (EHT). EHT is tightly controlled by multiple intrinsic and extrinsic mechanisms. Nevertheless, the molecular regulators restraining this process remain poorly understood. Here, it is uncovered that, one of the previously identified HEC signature genes, Nupr1, negatively regulates the EHT process. Nupr1 deletion in endothelial cells results in increased HSPC generation in the aorta-gonad-mesonephros region. Furthermore, single-cell transcriptomics combined with serial functional assays reveals that loss of Nupr1 promotes the EHT process by promoting the specification of hematopoiesis-primed functional HECs and strengthening their subsequent hematopoietic differentiation potential toward HSPCs. This study further finds that the proinflammatory cytokine, tumor necrosis factor 𝜶 (TNF-𝜶), is significantly upregulated in Nupr1-deficient HECs, and the use of a specific TNF-𝜶 neutralizing antibody partially reduces excessive HSPC generation in the explant cultures from Nupr1-deficient embryos. This study identifies a novel negative regulator of EHT and the findings indicate that Nupr1 is a new potential target for future hematopoietic stem cell regeneration research.

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Section: Resultsmentioning

confidence: 99%

Nupr1 Negatively Regulates Endothelial to Hematopoietic Transition in the Aorta‐Gonad‐Mesonephros Region

et al. 2023

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“… 39 Erythro-myeloid progenitors are thought to be derived from HECs present in both arterial and venous vascular bed of the yolk sac, 39 whereas in vivo and in vitro studies suggested that lymphoid potential is predominantly detected in the arterial vessels. 41 , 42 Recently, unbiased transcriptomic analyses have revealed that in general the arterial feature of HECs in yolk sac is much weaker than that in the AGM region 43 , 44 A study using Gja5-EGFP reporter as an arterial marker for functional assays showed that lymphoid potential can be detected in non-arterial yolk sac endothelial cells. 43 Recent studies have identified Neurl3-EGFP as a faithful marker for both intra-embryonic and yolk sac HECs.…”

Section: Transcriptomic Immunophenotypic and Functional Identificatio...mentioning

confidence: 99%

“… 41 , 42 Recently, unbiased transcriptomic analyses have revealed that in general the arterial feature of HECs in yolk sac is much weaker than that in the AGM region 43 , 44 A study using Gja5-EGFP reporter as an arterial marker for functional assays showed that lymphoid potential can be detected in non-arterial yolk sac endothelial cells. 43 Recent studies have identified Neurl3-EGFP as a faithful marker for both intra-embryonic and yolk sac HECs. The combination of Neurl3-EGFP and Unc5b-Tomato reporters revealed that yolk sac HECs contain 2 subpopulations with different level of arterial characteristics, and the lymphoid potential in the yolk sac was enriched in Neurl3-EGFP + Unc5b-Tomato + endothelial cells with an arterial-biased feature.…”

Section: Transcriptomic Immunophenotypic and Functional Identificatio...mentioning

confidence: 99%

“… 44 The different labeling efficiencies of arterial endothelial cells using different reporter mice and the distinct lymphoid induction strategies may underlie the seemingly conflicting conclusions. 43 , 44 In addition to Neurl3-EGFP, CD44 has been reported to enrich yolk sac endothelial cells with hemogenic potential at E10.0-E10.5. 43 The immunophenotypic PK44 cells in the yolk sac demonstrate short-term multilineage reconstitution capacity after in vitro incubation.…”

Section: Transcriptomic Immunophenotypic and Functional Identificatio...mentioning

confidence: 99%

“… 43 , 44 In addition to Neurl3-EGFP, CD44 has been reported to enrich yolk sac endothelial cells with hemogenic potential at E10.0-E10.5. 43 The immunophenotypic PK44 cells in the yolk sac demonstrate short-term multilineage reconstitution capacity after in vitro incubation. The yolk sac PK44 cells show endothelial- or hematopoietic-biased characteristic similar to those in the AGM region, but display transcriptomic features distinct from those in the AGM region, expressing yolk sac but not aortic endothelial cell markers such as Lyve1 and Stab2.…”

Section: Transcriptomic Immunophenotypic and Functional Identificatio...mentioning

confidence: 99%

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New insights into the endothelial origin of hematopoietic system inspired by “TIF” approaches

Hou,

Guo,

et al. 2024

Blood Science

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Hematopoietic stem progenitor cells (HSPCs) are derived from a specialized subset of endothelial cells named hemogenic endothelial cells (HECs) via a process of endothelial-to-hematopoietic transition during embryogenesis. Recently, with the usage of multiple single-cell technologies and advanced genetic lineage tracing techniques, namely, “TIF” approaches that combining transcriptome, immunophenotype and function/fate analyses, massive new insights have been achieved regarding the cellular and molecular evolution underlying the emergence of HSPCs from embryonic vascular beds. In this review, we focus on the most recent advances in the enrichment markers, functional characteristics, developmental paths, molecular controls, and the embryonic site-relevance of the key intermediate cell populations bridging embryonic vascular and hematopoietic systems, namely HECs and pre-hematopoietic stem cells, the immediate progenies of some HECs, in mouse and human embryos. Specifically, using expression analyses at both transcriptional and protein levels and especially efficient functional assays, we propose that the onset of Kit expression is at the HEC stage, which has previously been controversial.

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Hematopoietic Stem Cell Development in Mammalian Embryos

Hou,

Liu,

Yao

et al. 2023

Advances in Experimental Medicine and Biology

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Adult-repopulating lymphoid potential of yolk sac blood vessels is not confined to arterial endothelial cells

Cited by 8 publications

References 84 publications

Nupr1 Negatively Regulates Endothelial to Hematopoietic Transition in the Aorta‐Gonad‐Mesonephros Region

Nupr1 Negatively Regulates Endothelial to Hematopoietic Transition in the Aorta‐Gonad‐Mesonephros Region

New insights into the endothelial origin of hematopoietic system inspired by “TIF” approaches

Hematopoietic Stem Cell Development in Mammalian Embryos

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