LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage

Lee, Lydia K.; Ghorbanian, Yasamine; Wang, Wenyuan; Wang, Yanling; Kim, Yeon Joo; Weissman, Irving L.; Inlay, Matthew A.; Mikkola, Hanna

doi:10.1016/j.celrep.2016.10.080

Cited by 60 publications

(68 citation statements)

References 57 publications

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“…Taken together, these results strongly suggest that epigenetic priming by Dot1l in LEC progenitors, including both Tie2(+) and c-Kit(+) cells, during LEC differentiation is essential for the formation of mesenteric lymphatics. Moreover, given that HEs from the yolk sac are Lyve1 positive, whereas HEs from AGM are Lyve1 negative 41 , our findings also imply that Dot1l function in yolk-sac-derived HEs may have little effect on mesenteric LEC differentiation.…”

Section: Dot1l Function In C-kit(+) Hemogenic Ecs Is Required For Mesmentioning

confidence: 53%

Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function

et al. 2020

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Proper functioning of the lymphatic system is required for normal immune responses, fluid balance, and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure the correct formation and function of lymphatic vessels; however, the epigenetic modulators and mechanisms involved in this process are poorly understood. Here, we assess the regulatory role of mouse Dot1l, a histone H3 lysine (K) 79 (H3K79) methyltransferase, in lymphatic formation. Genetic ablation of Dot1l in Tie2(+) endothelial cells (ECs), but not in Lyve1(+) or Prox1(+) lymphatic endothelial cells (LECs) or Vav1(+) definitive hematopoietic stem cells, leads to catastrophic lymphatic anomalies, including skin edema, blood-lymphatic mixing, and underdeveloped lymphatic valves and vessels in multiple organs. Remarkably, targeted Dot1l loss in Tie2(+) ECs leads to fully penetrant lymphatic aplasia, whereas Dot1l overexpression in the same cells results in partially hyperplastic lymphatics in the mesentery. Genetic studies reveal that Dot1l functions in c-Kit(+) hemogenic ECs during mesenteric lymphatic formation. Mechanistically, inactivation of Dot1l causes a reduction of both H3K79me2 levels and the expression of genes important for LEC development and function. Thus, our study establishes that Dot1l-mediated epigenetic priming and transcriptional regulation in LEC progenitors safeguard the proper lymphatic development and functioning of lymphatic vessels.

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Section: Dot1l Function In C-kit(+) Hemogenic Ecs Is Required For Mesmentioning

confidence: 53%

Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function

et al. 2020

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“…In addition, like HSC, EMP require Runx1 for their emergence, providing further evidence that EMP emerge via an endothelial-to-hematopoietic transition (35, 36). Recent studies indicate that EMP and some HSC, but not primitive erythroid cells, emerge from LYVE-1+ endothelium (37). These results point to the distinct developmental origins of primitive- and EMP-derived hematopoiesis from posterior mesoderm (Figure 1).…”

Section: Ontogeny Of Erythropoiesismentioning

confidence: 99%

Interaction of the Macrophage and Primitive Erythroid Lineages in the Mammalian Embryo

Palis

2017

Front. Immunol.

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Two distinct forms of erythropoiesis, primitive and definitive, are found in mammals. Definitive erythroid precursors in the bone marrow mature in the physical context of macrophage cells in “erythroblastic islands.” In the murine embryo, overlapping waves of primitive hematopoietic progenitors and definitive erythro-myeloid progenitors, each containing macrophage potential, arise in the yolk sac prior to the emergence of hematopoietic stem cells. Primitive erythroblasts mature in the bloodstream as a semi-synchronous cohort while macrophage cells derived from the yolk sac seed the fetal liver. Late-stage primitive erythroblasts associate with macrophage cells in erythroblastic islands in the fetal liver, indicating that primitive erythroblasts can interact with macrophage cells extravascularly. Like definitive erythroblasts, primitive erythroblasts physically associate with macrophages through α4 integrin–vascular adhesion molecule 1-mediated interactions and α4 integrin is redistributed onto the plasma membrane of primitive pyrenocytes. Both in vitro and in vivo studies indicate that fetal liver macrophage cells engulf primitive pyrenocytes. Taken together, these studies indicate that several aspects of the interplay between macrophage cells and maturing erythroid precursor cells are conserved during the ontogeny of mammalian organisms.

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“…Although several studies suggested that HSCs may be produced from the YS [15][16][17][18] , engraftment experiments in avian models and transplantation studies in mice indicated an intraembryonic origin of HSCs [19][20][21][22] To date no explanation has been found to account for the difference in output of EHT that occurs in the YS versus AGM. It is not known whether there are intrinsic differences between the HEC of the two tissues or whether cell-extrinsic factors produced in the microenvironment drive HSC output in the AGM.…”

Section: Introductionmentioning

confidence: 99%

Single-cell atlas of major haematopoietic tissues sheds light on blood cell formation from embryonic endothelium

Shvartsman

Pavlovich

Oatley

et al. 2019

Preprint

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The Yolk Sac (YS) and Aorta-Gonad-Mesonephros (AGM) are two major haematopoietic regions during embryonic development. Interestingly, AGM is the only one generating haematopoietic stem cells (HSCs). To identify the difference between AGM and YS, we compared them using singlecell RNA sequencing between 9.5 and 11.5 days of mouse embryonic development and identified cell populations using CONCLUS, a new computational tool. The AGM was the only one containing neurons and a specific mesenchymal population, while the YS major component was an epithelial population expressing liver marker genes. In addition, the YS contained a major endothelial population expressing Stab2, a hyaluronan receptor, also highly expressed by liver endothelium. We demonstrated that the YS haematopoietic potential was restricted to Stab2negative cells and that ectopic expression of Stab2 could reduce blood cell formation from endothelium. Our results indicate that the AGM is a tissue more favourable to HSCs development than the YS because of its microenvironment and the nature of its endothelial cells.

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LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage

Cited by 60 publications

References 57 publications

Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function

Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function

Interaction of the Macrophage and Primitive Erythroid Lineages in the Mammalian Embryo

Single-cell atlas of major haematopoietic tissues sheds light on blood cell formation from embryonic endothelium

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