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A human iPSC-derived multilineage liver organoid model containing Kupffer cells to study human sepsis-associated liver dysfunction [hiPSC-EMP-KC-pKC]

ABSTRACT: To incorporate Kupffer cells into hiPSC-LOs, we differentiated erythro-myeloid progenitors (EMPs) from hiPSCs. We compares the gene expression profiles of hiPSC-EMPs with cord-blood hematopoietic stem and progenitor cells (CB-HSPCs); and EMP-generated Kupffer cells (EMP-KC) with human primary Kupffer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233538 | GEO | 2024/03/01

REPOSITORIES: GEO

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A human iPSC-derived multilineage liver organoid model containing Kupffer cells to study human sepsis-associated liver dysfunction [hiPSC-EMP-KC-pKC]

Project description:A human iPSC-derived multilineage liver organoid model containing Kupffer cells to study human sepsis-associated liver dysfunction [hiPSC-EMP-KC-pKC]

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A human iPSC-derived multilineage liver organoid model containing Kupffer cells to study human sepsis-associated liver dysfunction [KuLOs]

Project description:To recapitulate the pathology of human septic liver, we established hiPSC-derived liver organoids containing Kupffer cells (KuLOs). We performed gene expression profiling analysis using data obtained from RNA-seq of KuLOs with/without LPS/IFNr stimulation and the KuLOs during recovery after endotoxin elimination.

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Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors [RNA-seq]

Project description:Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of Ezh2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMP). Ezh2 activity is critical at the onset of the endothelial-to-hematopoietic transition generating EMPs but rapidly dispensable after that. We identified a lack of downregulation of Wnt signaling as the primary reason in the generation of non-functional EMPs. Together, our findings demonstrate a critical and specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.

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Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors [ATAC-seq]

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Single-cell sequencing of yolk sac and fetal liver hematopoietic progenitors

Project description:Erythro-myeloid progenitors (EMP) and their progeny were labeled with YFP in mouse embryos using genetic fate mapping (constitutive Csf1r-iCre;Rosa26-eYFP or inducible Csf1r-MeriCreMer;Rosa26-eYFP injected at embryonic day E8.5 with 4-hydroxytamoxifen). EMP-derived progenitors (Lin- Kit+ YFP+) were sorted by FACS for single-cell transcriptomic analysis using the MARS-Seq approach. The purpose was to uncover heterogeneity and differentiation trajectories of EMP by comparing their transcriptional status at different developmental timepoints (E9.5, E10.5 and E12.5) and across niches (yolk sac and fetal liver).

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Differentiation and specification of resident tissue macrophages [MARS-seq]

Project description:Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. The core macrophage transcriptional program initiated in pMacs, is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues. RNA-sequencing of sorted macrophage cell populations (Mac) and progenitors (EMP, pMac) from various tissues and collected at different time points, including technical and biological replicates

2016-08-08 | E-GEOD-81760 | biostudies-arrayexpress

Differentiation and specification of resident tissue macrophages [SMART-Seq2]

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RNAseq of Kupffer cells treated with IL2 and purifed Kupffer cells sub-populations (Kupffer Cell 1 and Kupffer Cell 2)

Project description:RNAseq of Kupffer cells treated with IL2 and purifed Kupffer cells sub-populations (Kupffer Cell 1 and Kupffer Cell 2)

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