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Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells

ABSTRACT: Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells

PROVIDER: PRJNA1054627 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27289013.fastq.gz	Fastqsanger.gz
	SRR27289014.fastq.gz	Fastqsanger.gz

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Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells

Project description:In mice, Kupffer cells (KCs) first derive from yolk sac (YS) hematopoietic progenitors prior to the emergence of the hematopoietic stem cell. To investigate human KC ontogeny, we recapitulated YS hematopoiesis from human pluripotent stem cells (hPSCs) and transplanted derivative macrophage progenitors into NSG mice previously humanized with hPSC-liver sinusoidal endothelial cells (LSECs). We demonstrate that hPSC-LSECs facilitate stable hPSC-YS-macrophage engraftment for at least 7 weeks. Single cell RNA sequencing of engrafted YS-macrophages revealed a homogenous MARCO-expressing KC gene signature and low expression of inflammatory macrophage genes. In contrast, human cord blood (CB)-derived macrophages generated grafts that contain multiple hematopoietic lineages in addition to KCs. Functional analyses showed that the engrafted KCs actively perform phagocytosis and erythrophagocytosis in vivo. Taken together, these findings demonstrate that it is possible to generate human KCs from hPSCs and show that the equivalent of the human YS hematopoietic programs represent enriched sources of progenitors for this lineage.

2024-08-09 | GSE250618 | GEO

Freshly isolated rat liver sinusoidal endothelial cells and Kupffer cells, LC-MSMS

Project description:Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) have important roles in liver homeostasis and host defense. Sharing the same microenvironment in the liver sinusoid, they form an effective scavenger cell system for removal of potentially harmful blood-borne substances. Unlike most other endothelia, LSECs are highly efficient in endocytosis of nanoparticles, including virus. Though controversial, LSECs have been reported to act as antigen presenting cells, thus contributing importantly to induction of immune tolerance in liver. There are also controversies about LSEC and KC specific markers, which may be due to overlapping cell functions, species differences, and/or problems with cell purification. We therefore used label-free proteomics to characterize and quantitatively compare proteome of freshly isolated, highly pure rat LSECs (SE-1/CD32b positive) and KCs (CD11b/c positive.We found that most immune genes expressed in KCs were also expressed in LSECs, albeit at a lower density, and they also have overlap in cell surface marker expression. Both cell types express high levels of scavenger receptors and immune lectins.

2020-11-11 | PXD012080 | Pride

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Comparison of gene expression between Human umbilical vein endothelial cells and Human liver sinusoidal endothelial cells

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