Characterization of quiescent adult liver stem cells and downstream lineages
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ABSTRACT:
PROVIDER: PRJNA270723 | ENA |
REPOSITORIES: ENA
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Project description:Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. By employing single-cell RNA-seq technology with weighted gene co-expression network analyses (WGCNA), we examined transcriptome features of distinct Krt19 lineage-tracing cell types isolated from Krt19CreERT; Rosa26R-GFP reporter mice, and identified gene expression signatures of quiescent and active adult LSCs, as well as their downstream lineage-restricted progenitors and terminally differentiation hepatocytes and cholangiocytes. Importantly, we discovered a novel cell surface LSC marker, CD63, as well as CD56, which distinguished active and quiescent LSCs. Furthermore, we confirmed that CD63+CD56- quiescent LSCs resided in Canals of Hering and peribiliary glands and that these cells could be activated by a combined action of VEGF and bFGF, and subsequently underwent terminal differentiation. These findings define an authentic adult liver stem cells compartment and highlight its contribution to liver homeostasis during pathophysiologic processes.
2018-10-29 | GSE64313 | GEO
Project description:Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. By employing single-cell RNA-seq technology with weighted gene co-expression network analyses (WGCNA), we examined transcriptome features of distinct Krt19 lineage-tracing cell types isolated from Krt19CreERT; Rosa26R-GFP reporter mice, and identified gene expression signatures of quiescent and active adult LSCs, as well as their downstream lineage-restricted progenitors and terminally differentiation hepatocytes and cholangiocytes. Importantly, we discovered a novel cell surface LSC marker, CD63, as well as CD56, which distinguished active and quiescent LSCs. Furthermore, we confirmed that CD63+CD56- quiescent LSCs resided in Canals of Hering and peribiliary glands and that these cells could be activated by a combined action of VEGF and bFGF, and subsequently underwent terminal differentiation. These findings define an authentic adult liver stem cells compartment and highlight its contribution to liver homeostasis during pathophysiologic processes.
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Differentiation of adult hematopoietic stem cells (HSC) constantly produces the cell types of the blood and immune system. The dynamics of this process and the hierarchy of downstream oligopotent stem cell differentiation remain controversial. Here we dissect hematopoietic progenitor populations in a minimally biased fashion using extensive single cell sampling from murine bone marrow. We characterize the HSC population, define its quiescent transcriptional program and validate it with label retaining assays and cytokine mediated stimulations. Analysis of initial HSC commitment defines marked bifurcation of erythroid/megakaryocytic cells from myeloid/lymphoid lineages. Unexpectedly, we find states that mix transcription of pre-myeloid and pre-lymphoid genes. This suggests a model in which more than one differentiation trajectory can link HSC to several cell types. Dendritic cells are thus linked with both monocyte and lymphocyte precursors. Our data support a model of hematopoiesis balancing relaxation of an HSC quiescent state, gradual bifurcations and trans-differentiation.
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Project description:Differentiation of adult hematopoietic stem cells (HSC) constantly produces the cell types of the blood and immune system. The dynamics of this process and the hierarchy of downstream oligopotent stem cell differentiation remain controversial. Here we dissect hematopoietic progenitor populations in a minimally biased fashion using extensive single cell sampling from murine bone marrow. We characterize the HSC population, define its quiescent transcriptional program and validate it with label retaining assays and cytokine mediated stimulations. Analysis of initial HSC commitment defines marked bifurcation of erythroid/megakaryocytic cells from myeloid/lymphoid lineages. Unexpectedly, we find states that mix transcription of pre-myeloid and pre-lymphoid genes. This suggests a model in which more than one differentiation trajectory can link HSC to several cell types. Dendritic cells are thus linked with both monocyte and lymphocyte precursors. Our data support a model of hematopoiesis balancing relaxation of an HSC quiescent state, gradual bifurcations and trans-differentiation.
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