Single cell analysis of human fetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
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PROVIDER: PRJNA540429 | ENA |
REPOSITORIES: ENA
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Project description:The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human fetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of fetal liver and maintain a unique transcriptional profile distinct from fetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogenicity within the EpCAM+ population of freshly isolated fetal and adult human liver reveals diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolated fetal HHyPs and confirmed their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.
2019-05-21 | GSE130473 | GEO
Project description:The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogeneity within the EpCAM+ population of freshly isolated foetal and adult human liver identifies diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolate foetal HHyPs and confirm their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.
| S-EPMC6659636 | biostudies-literature
Project description:Human lymphopoiesis is a dynamic life-long process that starts in utero at 6 weeks gestation; however developmental pathways defining fetal lymphopoiesis are largely unexplored. While the first committed B-progenitor in normal human bone marrow (BM) is a CD10+ve ProB-progenitor, the identification of a CD10-ve B-progenitor (Pre/ProB progenitor) in cord blood suggests there may be a second B-lymphoid development program in fetal life. Here, we provide a comprehensive analysis of the fetal B-cell developmental hierarchy and report the presence of both PreProB- and ProB-progenitors in fetal tissues and describe their ontogeny, molecular and functional characteristics. PreProB- and ProB-progenitors appear early in the first trimester in fetal liver, followed by a sustained second wave of B-progenitor development in fetal BM, where together they form >40% of the total HSC/progenitor pool. Unexpectedly, one-third of the B-progenitors (13±1% of lin-CD34+ cells) are CD10-ve PreProB-progenitors while, by contrast, PreProB-progenitors are virtually undetectable in adult BM. Single-cell transcriptomics and functional assays place PreProB- upstream of ProB-progenitors, identifying them as the first B-lymphoid restricted progenitor in human fetal life. Fetal BM PreProB- and ProB-progenitors both give rise solely to B-lineage cells yet they are transcriptionally distinct. PreProB- unlike ProB-progenitors, continue to express a number of key myeloid and stem cell genes and share some transcriptomic signatures with CD10-ve B-progenitor infant acute lymphoblastic leukemia blast cells. Our data identify PreProB-progenitors as the earliest B-lymphoid restricted progenitor in human fetal life, and suggest that this fetal-restricted committed B-progenitor might provide a permissive cellular context for prenatal B-progenitor leukemia initiation.
2019-08-06 | GSE122989 | GEO
Project description:We describe the proteomic composition of the secretome of fetal and adult hematopoietic progenitors during MLL-rearranged (MLLr) leukemia initiation as well as the pre-leukemic cells’ secretion response to the treatment with Fibulin (Fbln1) and/or Fibronectin (Fn1) using data-independent acquisition mass spectrometry analysis.
2024-04-02 | PXD049014 | Pride
Project description:This project is to identify plasma glycoprotein markers for hepatobiliary cancers
2019-11-12 | PXD013629 | Pride
Project description:Single-cell RNA sequencing of human peripheral blood progenitors captures early mast cell differentiation
| PRJNA764206 | ENA
Project description:ATAC-Sequencing of human fetal PreProB and ProB progenitors.
| PRJNA507171 | ENA
Project description:Neuroendocrine neoplasms of the gallbladder and liver occur rarely in dogs and humans. A recent reclassification of human neuroendocrine neoplasms by the World Health Organization has refined categorization of these tumors by morphology, replicative indices, and molecular signatures. In humans, these factors correlate with survival outcomes. Improved characterization of these tumors is needed in dogs to identify diagnostic biomarkers and determine therapeutic strategies. To achieve this objective, the proteome of 3 canine hepatobiliary neoplasms was compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Thirty-two upregulated and 121 downregulated differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasm samples. Among the upregulated proteins is galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression in humans. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia in human medicine. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
2023-03-11 | PXD028822 | Pride
Project description:We describe the proteomic composition of the extracellular environment of fetal and adult hematopoietic progenitors by data-independent acquisition mass spectrometry analysis.
2024-04-02 | PXD042251 | Pride
Project description:While others have reported that fetal liver contains a population of endothelial progenitors based on expression of cell surface markers or culture assays, this is the first proof of a CD31+Sca1+ progenitor by demonstrating highly efficient in vivo angiogenesis and a direct connection to the host vasculature. We have developed a novel isolation method based on collagenase digestion and culture on a fetal liver-derived feeder layer and demonstrate that the feeder cells or their supernatants are required for endothelial progenitor survival and proliferation. Proteogenomic profiling of the endothelial progenitors and the feeder cells was done with tandem mass spectrometry proteomics using MudPIT and gene transcript expression profiling using high density DNA microarrays. This approach identified a number of gene transcripts, proteins and candidate growth factor pathways that are likely to be involved in endothelial progenitor growth, differentiation and angiogenesis. Keywords = LEP - Liver Endothelial progenitor Keywords = Feeder Cells Keywords = Angiogenesis Keywords = Proteogenomics Keywords = Growth Factors Keywords = Fetal liver Keywords: parallel sample
2005-03-01 | GSE1727 | GEO