Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA305280 | ENA |
REPOSITORIES: ENA
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Project description:Human pluripotent stem cells (hPSCs) offer a unique cellular model to study lineage specifications of the primary germ layers during human development. We profiled single-cell RNA-seq (scRNA-seq) on four lineage-specific progenitor cells derived from hESCs. Our scRNA-seq analyses revealed each type of progenitors display various extend of heterogeneity. Specifically, definitive endoderm cells (DECs) not only show a greater degree of heterogeneity, but are also enriched in metabolic signatures. Followed by detailed temporal scRNA-seq profiling along DEC differentiation, we reconstructed a differentiation trajectory using a novel statistical pipeline named Wave-Crest. Wave-Crest further identifies candidate regulators during the transitioning phase from Brachyury (T)+ mesendoderm towards CXCR4+ DEC state. To functionally test identified novel regulators; we generated a live cell monitoring system, a T-2A-EGFP knock-in reporter cell line via CRISPR/CAS9. We demonstrated that, among the top candidate genes, KLF8 plays a pivotal role modulating mesendoderm to DEC differentiation. In this submission, 1810 raw fastq files are provided; 212 are re-analysis from GSE64016. Four expected count matrices are provided - 1) 1018 single cells from snapshot progenitors; 2) 758 single cells from time couse profiling; 3) 19 bulk RNA-seq sample from snapshot progenitors; 4) 15 bulk RNA-seq sample from time course profiling. Total 1018 single cells from snapshot progenitors and 758 single cells from time couse profiling. Matchd population bulk RNA-seq samples for both the progenitors snapshot (19 samples) and time course profiling (15 samples) also included in this submission. These data set are used to detect the transitioning phase from mesendoderm to definitive endoderm.
2016-07-21 | E-GEOD-75748 | biostudies-arrayexpress
Project description:Human pluripotent stem cells (hPSCs) offer a unique cellular model to study lineage specifications of the primary germ layers during human development. We profiled single-cell RNA-seq (scRNA-seq) on four lineage-specific progenitor cells derived from hESCs. Our scRNA-seq analyses revealed each type of progenitors display various extend of heterogeneity. Specifically, definitive endoderm cells (DECs) not only show a greater degree of heterogeneity, but are also enriched in metabolic signatures. Followed by detailed temporal scRNA-seq profiling along DEC differentiation, we reconstructed a differentiation trajectory using a novel statistical pipeline named Wave-Crest. Wave-Crest further identifies candidate regulators during the transitioning phase from Brachyury (T)+ mesendoderm towards CXCR4+ DEC state. To functionally test identified novel regulators; we generated a live cell monitoring system, a T-2A-EGFP knock-in reporter cell line via CRISPR/CAS9. We demonstrated that, among the top candidate genes, KLF8 plays a pivotal role modulating mesendoderm to DEC differentiation. In this submission, 1810 raw fastq files are provided; 212 are re-analysis from GSE64016. Four expected count matrices are provided - 1) 1018 single cells from snapshot progenitors; 2) 758 single cells from time couse profiling; 3) 19 bulk RNA-seq sample from snapshot progenitors; 4) 15 bulk RNA-seq sample from time course profiling.
2016-07-21 | GSE75748 | GEO
Project description:Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in stem cell biology. This knowledge will aid in the targeted differentiation and growth of stem cells, but also in the discovery of the basis of cellular plasticity and of how tissue programming can be controlled. The liver and pancreas share many aspects of their early development, being both specified in the same region of the endoderm, and, possibly, originating from a common progenitor. However, how pancreas versus liver cell fate decision occurs during embryogenesis and the molecular basis of this cellular plasticity are poorly understood. Here, we use RNA-Seq to define the molecular identity of liver and pancreas progenitors directly in mouse embryos and to investigate the mechanisms regulating the emergence of liver or pancreas as alternative fates from the endoderm. Progenitor cell-specific RNA was obtained from mouse Prox1-EGFP-labeled embryonic cells isolated by FACS at distinct developmental stages, before and after the onset of organogenesis. By integrating the temporal and spatial gene expression profiles, we found mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the non-canonical Wnt pathway as a potential developmental regulator of the pancreas versus liver fate decision, being expressed in the foregut endoderm, before the cell fate choice is made, and then maintained in pancreas progenitors but absent in hepatic progenitors. Moreover, when assayed in Xenopus embryos, the non-canonical Wnt pathway is able to promote pancreatic fate and repress hepatic fate in the endoderm, suggesting an ancient mechanism for controlling pancreas versus liver fate choice. We expect that this knowledge will be key to formulate reprogramming strategies to convert adult hepatic cells into pancreatic cells as a cell-based therapeutic approach for diabetes. We performed sequencing-based expression profiling (RNA-Seq) of hepatic and pancreatic progenitors in the mouse at two distinct developmental stages.
2013-09-11 | E-GEOD-40823 | biostudies-arrayexpress
Project description:Metabolism is vital to cellular function and tissue homeostasis during human lung development. In utero, embryonic pluripotent stem cells undergo endodermal differentiation towards a lung progenitor cell fate that can be mimicked in vitro using induced human pluripotent stem cells (hiPSCs) to study genetic mutations. To identify differences between wild type and surfactant protein B (SFTPB)-deficient cell lines during endoderm specification towards lung, we used an untargeted metabolomics approach to evaluate the developmental changes in metabolites. We found that the metabolites most enriched during the differentiation from pluripotent stem cell to lung progenitor cell, regardless of cell line, were sphingomyelins and phosphatidylcholines, two important lipid classes in fetal lung development. The SFTPB mutation had no metabolic impact on early endodermal lung development. The identified metabolite signatures during lung progenitor cell differentiation may be utilized as biomarkers for normal embryonic lung development.
2021-06-29 | ST002055 | MetabolomicsWorkbench
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
2021-07-01 | MODEL2105030001 | BioModels
Project description:Endoderm cells undergo a sequence of fate choices to generate insulin-secreting M-NM-2 cells. Studies of chromatin transitions during this process have been limited to the pancreatic progenitor stage that can be reconstituted from stem cells in vitro, with a gap in understanding the induction of endocrine cells. To address this, we established conditions for isolating endoderm cells, pancreatic progenitors, and endocrine cells from different staged embryos and performed genome wide analysis of the H3K27me3 mark of the repressive Polycomb complex. During the transition from endoderm to pancreas progenitors and during the transition from pancreas progenitors to endocrine cells, genes that lose the H3K27me3 mark typically encode transcriptional regulators, whereas genes that acquire the mark typically are involved in cell biology morphogenesis. Precocious depletion of the EZH2, a H3K27 methylase, at the pancreas progenitor stage enhanced the production of endocrine cells, leading to a later increase in pancreatic beta cells. Similarly, pharmacologic inhibition of EZH2 in embryonic pancreatic tissue explants and human embryonic stem cell cultures led to an increase in endocrine progenitors in vitro. These findings reveal a repeating target gene pattern in H3K27me3 dynamics and provide a means to modulate M-NM-2 cell development from stem cells. Analyzed five FACS-sorted tissues in early mouse embryo; for each tissue we sequenced H3K27me3 and input; no replicates
2014-07-28 | E-GEOD-56617 | biostudies-arrayexpress
Project description:Endoderm cells undergo a sequence of fate choices to generate insulin-secreting β cells. Studies of chromatin transitions during this process have been limited to the pancreatic progenitor stage that can be reconstituted from stem cells in vitro, with a gap in understanding the induction of endocrine cells. To address this, we established conditions for isolating endoderm cells, pancreatic progenitors, and endocrine cells from different staged embryos and performed genome wide analysis of the H3K27me3 mark of the repressive Polycomb complex. During the transition from endoderm to pancreas progenitors and during the transition from pancreas progenitors to endocrine cells, genes that lose the H3K27me3 mark typically encode transcriptional regulators, whereas genes that acquire the mark typically are involved in cell biology morphogenesis. Precocious depletion of the EZH2, a H3K27 methylase, at the pancreas progenitor stage enhanced the production of endocrine cells, leading to a later increase in pancreatic beta cells. Similarly, pharmacologic inhibition of EZH2 in embryonic pancreatic tissue explants and human embryonic stem cell cultures led to an increase in endocrine progenitors in vitro. These findings reveal a repeating target gene pattern in H3K27me3 dynamics and provide a means to modulate β cell development from stem cells.
2014-07-28 | GSE56617 | GEO
Project description:Anterior mesoderm (AM) and definitive endoderm (DE) progenitors represent the earliest embryonic cell types that are specified during germ layer formation at the primitive streak (PS) of the mouse embryo. Genetic experiments indicate that both lineages segregate from Eomes expressing progenitors in response to different NODAL signaling levels. However, the precise spatiotemporal pattern of the emergence of these cell types and molecular details of lineage segregation remain unexplored. We combined genetic fate labeling and imaging approaches with single cell RNA sequencing (scRNA-seq) to follow the transcriptional identities and define lineage trajectories of Eomes dependent cell types. Accordingly, all cells moving through the PS during the first day of gastrulation express Eomes AM and DE specification occurs before cells leave the PS from Eomes positive progenitors in a distinct spatiotemporal pattern. ScRNA-seq analysis further suggest the immediate and complete separation of AM and DE lineages from Eomes expressing cells as last common bipotential progenitor.
2020-12-07 | GSE151824 | GEO
Project description:During mammalian pre-implantation development, the cells of the blastocyst’s inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra-embryonic tissues, respectively. Extra-embryonic endoderm differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here we use this GATA-inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo-derived extra-embryonic endoderm (XEN) cells. Using mass spectrometry-based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and extra-embryonic endoderm differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin-modifying enzymes, the re-organization of membrane trafficking machinery and the breakdown of cell-cell adhesion are successive steps of the extra-embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time-resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes.
2015-06-13 | PXD001901 | Pride
Project description:Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in stem cell biology. This knowledge will aid in the targeted differentiation and growth of stem cells, but also in the discovery of the basis of cellular plasticity and of how tissue programming can be controlled. The liver and pancreas share many aspects of their early development, being both specified in the same region of the endoderm, and, possibly, originating from a common progenitor. However, how pancreas versus liver cell fate decision occurs during embryogenesis and the molecular basis of this cellular plasticity are poorly understood. Here, we use RNA-Seq to define the molecular identity of liver and pancreas progenitors directly in mouse embryos and to investigate the mechanisms regulating the emergence of liver or pancreas as alternative fates from the endoderm. Progenitor cell-specific RNA was obtained from mouse Prox1-EGFP-labeled embryonic cells isolated by FACS at distinct developmental stages, before and after the onset of organogenesis. By integrating the temporal and spatial gene expression profiles, we found mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the non-canonical Wnt pathway as a potential developmental regulator of the pancreas versus liver fate decision, being expressed in the foregut endoderm, before the cell fate choice is made, and then maintained in pancreas progenitors but absent in hepatic progenitors. Moreover, when assayed in Xenopus embryos, the non-canonical Wnt pathway is able to promote pancreatic fate and repress hepatic fate in the endoderm, suggesting an ancient mechanism for controlling pancreas versus liver fate choice. We expect that this knowledge will be key to formulate reprogramming strategies to convert adult hepatic cells into pancreatic cells as a cell-based therapeutic approach for diabetes.
2013-09-11 | GSE40823 | GEO