Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171560 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Hematopoietic differentiation from human pluripotent stem cell in vitro is an important approach for the research of hematopoietic stem cell regeneration. Small molecules that can maintenance low ROS level and inhibit cell apoptosis or autophagy are benifit for the maintenance or expansion of hematopoietic stem cells. Lipoic acid (ALA) as a small antioxidant molecule can regulate the ROS level and apoptosis of cells. This study found that lipoic acid promoted the production of hemogenic endothelial cells and hematopoietic progenitor cells. Transcriptome analysis of hemogenic endothelial cells showed that ALA upregulated the endothelial to hematopoietic transition (EHT) related genes and downregulated the EHT negative regulated genes. ALA also up-regulated ROS and apoptosis related genes to inhibit the apoptosis of hematopoietic stem/progenitor cells.These results indicated that ALA might have an important role in the regeneration of hematopoietic stem progenitor cell in vitro.
2020-07-14 | GSE144307 | GEO
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:Recently, we identified and characterized specific endothelial progenitors with varying hemogenic potential during human pluripotent stem cell differentiation. Based on these studies we established a platform on which we can manipulate NOTCH signaling on these subsets to elucidate the specific role of this signaling pathway during hemogenic endothelial specification, endothelial-to-hematopoietic transition, and definitive hematopoietic specification.
2018-03-09 | GSE95028 | GEO
Project description:The differentiation of human embryonic stem cells to hematopoietic lineages initiates with the specification of hemogenic endothelium, a transient specialized endothelial precursor of all blood cells.Unfortunately, absence of hemogenic endothelium-specific markers as well as lack of consensus in the timing of hemogenic potential analysis and methodologies used to study the hematopoietic potential of this precursor prevents reaching clear and definite conclusions. Here, we demonstrate that the hemogenic potential of the endothelium precursor population sharply decline over the course of the differentiation process. Poly(A) RNA-sequencing on CD31+CD144+ population at day 6, day 8 and day 10 of EB diffferentiation with or without the addition of cytokines. Comparasion with hematopoietic committed population CD31+CD144- from day 10 of EB differentiation.
2018-10-25 | GSE109648 | GEO
Project description:Human embryonic stem cells (hESCs) are a powerful tool for modeling regenerative therapy. To search for the genes that promote hematopoietic development from human pluripotent stem cell, we overexpressed a list of hematopoietic regulator genes in human pluripotent stem cell-derived CD34+CD43- endothelial cells (ECs) enriched in hemogenic endothelium. Among genes tested, only SOX17, a gene encoding a transcription factor of the SOX family, promoted cell growth and supported expansion of CD34+CD43+CD45-/low cells expressing a hemogenic endothelial maker VE-cadherin. SOX17 was highly expressed in CD34+CD43- ECs but at a low level in CD34+CD43+CD45- pre-hematopoietic progenitor cells (pre-HPCs) and CD34+CD43+CD45+ HPCs. SOX17-overexpressing cells formed sphere-like colonies and generated few hematopoietic progenies. However, they retained hemogenic potential and gave rise to hematopoietic progenies upon inactivation of SOX17. Global gene expression analyses revealed that the CD34+CD43+CD45-/low cells expanded upon overexpression of SOX17 are hemogenic endothelium-like cells developmentally placed between ECs and pre-HPCs. Of interest, SOX17 also reprogrammed both pre-HPCs and HPCs into hemogenic endothelium-like cells. Genome-wide mapping of SOX17 revealed that SOX17 directly activates transcription of key regulator genes for vasculogenesis, hematopoiesis, and erythrocyte differentiation. Depletion of SOX17 in CD34+CD43- ECs severely compromised their hemogenic activity. These findings suggest that SOX17 plays a critical role in priming hemogenic potential in ECs, thereby regulates hematopoietic development from hESCs. This SuperSeries is composed of the SubSeries listed below.
2012-12-14 | GSE38156 | GEO
Project description:In vitro generation of mature neutrophils from human induced pluripotent stem cells (iPSCs) requires hematopoietic progenitor development followed by myeloid differentiation. The purpose of our studies was to extensively characterize this process, focusing on the critical window of development between hemogenic endothelium, hematopoietic stem/progenitor cells (HSPCs), and myeloid commitment, to identify associated regulators and markers that might enable the stem cell field to improve the efficiency and efficacy of iPSC hematopoiesis. We utilized a 4-stage differentiation protocol involving: embryoid body (EB) formation (Stage-1); EB culture with hematopoietic cytokines (Stage-2); HSPC expansion (Stage-3); and neutrophil maturation (Stage-4). CD34+CD45- putative hemogenic endothelial cells were observed in Stage-3 cultures, and expressed VEGFR-2/Flk-1/KDR and VE-cadherin endothelial markers, GATA-2, AML1/RUNX1, and SCL/TAL1 transcription factors, and endothelial/HSPC-associated microRNAs miR-24, miR-125a-3p, miR-126/126*, and miR-155. Upon further culture, CD34+CD45- cells generated CD34+CD45+ HSPCs that produced hematopoietic CFUs. Mid-Stage-3 CD34+CD45+ HSPCs exhibited increased expression of GATA-2, AML1/RUNX1, SCL/TAL1, C/EBPα, and PU.1 transcription factors, but exhibited decreased expression of HSPC-associated microRNAs, and failed to engraft in immune-deficient mice. Mid-stage-3 CD34-CD45+ cells maintained PU.1 expression and exhibited increased expression of hematopoiesis-associated miR-142-3p/5p and a trend towards increased miR-223 expression, indicating myeloid commitment. By late Stage-4, increased CD15, CD16b, and C/EBPε expression were observed, with 25-65% of cells exhibiting morphology and functions of mature neutrophils. These studies demonstrate that hematopoiesis and neutrophil differentiation from human iPSCs recapitulates many features of embryonic hematopoiesis and neutrophil production in marrow, but reveals unexpected molecular signatures that may serve as a guide for enhancing iPSC hematopoiesis. miRNA expression profiles were analyzed in iNC-01-3 and iNC-01-4 induced pluripotent stem cell lines at day 0 (undifferentiated iPSCs), day 18 of differentiation (embryoid bodies), and in 3 FACS-sorted cell populations at day 22 of differentiation (CD34+CD45- cells, CD34+CD45+ cells, and CD34-CD45+ cells). Comparative CT analysis was normalized to U6 snRNA and RNU48 control RNAs relative to expression in undifferentiated iPSCs. Data includes 2 files for each sample, one for the card A array and one for the card B array. This includes a total of 32 data files consisting of: 5 replicates for undifferentiated iPSCs (10 files), 2 replicates for EB (4 files), 3 replicates for CD34+CD45- (6 files), 3 replicates for CD34+CD45+ (6 files), and 3 replicates for CD34-CD45+ (6 files).
2016-01-12 | E-GEOD-69503 | biostudies-arrayexpress
Project description:It has now been well established that hematopoietic stem and progenitor cells originate from a specialised subset of endothelium termed hemogenic endothelium (HE) via an endothelial-to-hematopoietic transition. However, the molecular mechanisms determining which endothelial progenitors possess or not this hemogenic potential is currently unknown. In this study, we investigated the changes in hemogenic potential in endothelial progenitors at the early stages of embryonic development. We use a microarray approach to profile the genes regulated between E7.5 and E8.5 embryonic day in the ETV2+FLK1+CD41- compartment. Cells were sorted based on ETV2::GFP+/FLK1+/CD41- immunophenotype from ETV2::GFP embryos at E7.5 and E8.5 developmental stage in triplicates
2016-05-31 | E-GEOD-64377 | biostudies-arrayexpress
Project description:Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6 that efficiently induces endothelial-like precursor cells with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1 and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent/specifying hematopoietic stem cell gene expression profiles and cell surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate hematopoietic colonies in vitro. Thus, we have shown that a simple combination of transcription factors is sufficient to induce a complex, dynamic and multi-step developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem/progenitor cells as well as more differentiated blood products. mRNA-seq profiling on populations generated after transduction with Gata2, Gfi1b, cFos and Etv6 at day 20 and day 35.
2013-06-13 | E-GEOD-47497 | biostudies-arrayexpress
Project description:We report a novel technique to reprogram human fibroblasts into endothelial and smooth muscle cells using partial iPSC reprogramming and chemically defined media. Using appropriate media conditions for differentiation of human pluripotent cells to CD34+ vascular progenitor cells, we show that temporary expression of pluripotent transcription factors and treatment with chemically-defined media, will induce differentiation of human fibroblasts to CD34+ vascular progenitor cells. Sorted CD34+ cells can then be directed to differentiate into vascular endothelial cells expressing a variety of smooth muscle markers. We have assessed the global DNA methylation (Illumina Infinium HD 450K DNA methylationBeadChips) and transcriptional (Illumina HT12v4 Gene Expression Bead Array) profiles of transdifferentiated endothelial cells and smooth muscle, human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC) differentiated CD34+ angioblasts, hESCs, hiPSC, primary smooth muscle and primary human umbilical vein endothelial cells using microarrays.
2012-09-18 | E-GEOD-40909 | biostudies-arrayexpress
Project description:In vitro generation of mature neutrophils from human induced pluripotent stem cells (iPSCs) requires hematopoietic progenitor development followed by myeloid differentiation. The purpose of our studies was to extensively characterize this process, focusing on the critical window of development between hemogenic endothelium, hematopoietic stem/progenitor cells (HSPCs), and myeloid commitment, to identify associated regulators and markers that might enable the stem cell field to improve the efficiency and efficacy of iPSC hematopoiesis. We utilized a 4-stage differentiation protocol involving: embryoid body (EB) formation (Stage-1); EB culture with hematopoietic cytokines (Stage-2); HSPC expansion (Stage-3); and neutrophil maturation (Stage-4). CD34+CD45- putative hemogenic endothelial cells were observed in Stage-3 cultures, and expressed VEGFR-2/Flk-1/KDR and VE-cadherin endothelial markers, GATA-2, AML1/RUNX1, and SCL/TAL1 transcription factors, and endothelial/HSPC-associated microRNAs miR-24, miR-125a-3p, miR-126/126*, and miR-155. Upon further culture, CD34+CD45- cells generated CD34+CD45+ HSPCs that produced hematopoietic CFUs. Mid-Stage-3 CD34+CD45+ HSPCs exhibited increased expression of GATA-2, AML1/RUNX1, SCL/TAL1, C/EBPα, and PU.1 transcription factors, but exhibited decreased expression of HSPC-associated microRNAs, and failed to engraft in immune-deficient mice. Mid-stage-3 CD34-CD45+ cells maintained PU.1 expression and exhibited increased expression of hematopoiesis-associated miR-142-3p/5p and a trend towards increased miR-223 expression, indicating myeloid commitment. By late Stage-4, increased CD15, CD16b, and C/EBPε expression were observed, with 25-65% of cells exhibiting morphology and functions of mature neutrophils. These studies demonstrate that hematopoiesis and neutrophil differentiation from human iPSCs recapitulates many features of embryonic hematopoiesis and neutrophil production in marrow, but reveals unexpected molecular signatures that may serve as a guide for enhancing iPSC hematopoiesis.
2016-01-12 | GSE69503 | GEO