Human arterial endothelial cells from pluripotent stem cells for in vitro hematopoiesis and lymphopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA900196 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22254223.fastq.gz | Fastqsanger.gz | |||
| SRR22254224.fastq.gz | Fastqsanger.gz | |||
| SRR22254225.fastq.gz | Fastqsanger.gz | |||
| SRR22254226.fastq.gz | Fastqsanger.gz | |||
| SRR22254227.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Arterial endothelial cells (AECs) are the founder cell for intraembryonic haematopoiesis. Here, we report a method for the efficient generation of human haemogenic DLL4+ AECs from pluripotent stem cells (PSC). Time-series single cell RNA-sequencing revealed the dynamic evolution of haematopoiesis and lymphopoiesis from endothelial stage, generating cell types with counterparts present in early human embryos. Our study describes an efficient method for producing lymphoid cells and provides insights into their endothelial and haematopoietic ontogeny, paving a new path to investigations of the human blood system.
2024-08-01 | GSE217705 | GEO
Project description:Human pluripotent stem cells (hPSCs) provide a powerful platform for studying the dynamic molecular network towards hematopoiesis. To date, a comprehensive roadmap at single-cell resolution for hPSC-derived hematopoietic differentiation has not been established. Here, we performed extensive single-cell transcriptomic analyses to map fate choices and gene expression programs during hematopoietic differentiation of hPSCs and identified strategies to improve the quantity and quality of hPSC-derived hematopoietic cells. By focusing specifically on cell populations and molecular events involved in endothelial-to-hematopoietic transition (EHT), the EHT was identified accompanying by a decline in aerobic metabolism and providing hypoxia in vitro enhances arterial and hematopoietic differentiation. Furthermore, arterial endothelial cells are validated as a critical regulator of definitive hematopoietic progenitor specification. Collectively, our study provides benchmark datasets to understand the origins of human hematopoiesis and presents an advance for guiding the generation of functional hematopietic cells in vitro for clinical applications.
2021-09-22 | GSE145859 | GEO
Project description:We identified that the coordinated expression of exogenous transcription factors(Lhx2, Hoxa9, and Runx1), efficiently guides PSC-derived hematopoietic progenitors (iHPC) preferentially towards B cell lineage commitment, which successfully regenerate B lymphopoiesis in B-cell deficient animals. Of note, the abundancy of in vivo lymphopoiesis includes pro/pre-B progenitors, immature B cells, and all subsets of mature B1a, B1b, FO B and MZ B reconstitution in vivo. We performed single-cell RNA-Seq using the sorted GFP+CD45+ Lin- cells from the bone marrow of recipients at day 7.5 after iHPC transplantation.
2021-12-16 | GSE180319 | GEO
Project description:We identified that the coordinated expression of exogenous transcription factors efficiently guides PSC-derived hematopoietic progenitors (iHPC) preferentially towards B cell lineage commitment, which successfully regenerate B lymphopoiesis in B-cell deficient animals. Of note, the abundancy of in vivo lymphopoiesis includes pro/pre-B progenitors, immature B cells, and all subsets of mature B1a, B1b, FO B and MZ B reconstitution in vivo. We performed BCR deep sequencing using the sorted naive follicular B cells from the spleen of one recipient at week 4 after iHPC transplantation and one C57BL/6 mouse as control.
2021-12-16 | GSE180318 | GEO
Project description:Identification of the regulators that lead to arterial specification with definitive hematopoietic potential should help to design strategies to recapitulate HSC development from human pluripotent stem cells (hPSCs). Here, using ETS1 conditional H1 hESC line, we found that ETS1 induction at the mesodermal stage of differentiation dramatically enhances the arterial specification in hPSC cultures and formation of DLL4+CXCR4+/- arterial HE with lymphoid potential and the capacity to produce red blood cells with high expression of BCL11a and b-globin. ETS1 effect was mediated through upregulation of NOTCH signaling. Together, these findings demonstrated that promotion of arterial specification in cultures could aid in generation of definitive hematopoiesis from hPSCs.
2018-03-09 | GSE96815 | GEO
Project description:Acute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Here we show that leukemic cells turn-off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow. ALL and AML cells express lymphotoxin-a1b2 and activate LTbR signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. Genetic or pharmacologic disruption of LTbR signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and extends survival of transplant recipients significantly. These studies demonstrate that acute leukemias exploit physiological mechanisms governing hematopoietic output as a strategy for gaining competitive advantage. Our studies also reveal that disrupting the cross-talk between leukemia cells and bone marrow niche cells, and specifically the LTbR pathway, offers new therapeutic opportunities.
2023-01-02 | GSE221243 | GEO
Project description:IKKa, a major regulator of noncanonical and canonical NF-kB pathways, is essential for B-lymphocyte maturation and secondary lymph organ formation. No evidence of IKKa regulating early B cell development currently exists. Here we found reduced pre-pro-B and pro-B cells but increased myeloid-erythroid lineages in the bone marrow (BM) of knockin mice expressing reduced and kinase-dead IKKa (KA/KA). The KA/KA BM cells recaptured their defects in wild-type recipients and KA/KA fetal liver displayed reduced B cells but increased progenitors. IKKa inactivation impaired both NF-kB pathways and deregulated expression of many genes required for early B cell commitment and hematopoiesis, including downregulated Pax5, IRF4, and Ikaros expression, but increased C/EBPa, GATA1, and Stat3 levels. Reintroduced combined NF-kB components, Pax5, and IKKa promoted BM B cell differentiation and repressed myeloid-erythroid lineages. Our studies revealed a new function of IKKa in a coordinated development process of B-lineage and erythroid-myeloid lineages during hematopoiesis via multiple pathways. Microarray analysis was performed on RNA isolated from the BM of B220+ cells isolated from 4-week old WT and KA/KA mice using affymetrix mouse 430 2.0 array chip, containing 45,000 genes, at the Laboratory of Molecular Technology SAIC-Frederick. Data were normalized, and log2 transformations were generated using Partek software (St. Louis, MO, USA).
2011-07-02 | E-GEOD-30363 | biostudies-arrayexpress
Project description:Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. We demonstrate in small pre-B cells, that the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 differentially regulated over 7000 genes including repressing proliferative and inducing differentiation programs. However, BRWD1 did not regulate expression of transcription factors required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations had B cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1-/- mice. These data indicate that in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B cell development.
2018-08-11 | GSE103057 | GEO
Project description:Hematopoiesis occurs within a unique bone marrow (BM) microenvironment which consists of various niche cells, cytokines, growth factors and extracellular matrix components. These multiple components directly or indirectly regulate the maintenance and differentiation of hematopoietic stem cells (HSCs). Here we report that Bap1 in BM mesenchymal stromal cells (MSCs) is critical for the maintenance of HSCs and B lymphopoiesis. Mice lacking Bap1 in MSCs show aberrant differentiation of hematopoietic stem and progenitor cells, impaired B lymphoid differentiation, and expansion of myeloid lineages. Mechanistically, Bap1 loss in distinct endosteal MSCs, expressing Prx1 but not Lepr, leads to aberrant expression of genes affiliated with BM niche functions. Bap1 deficiency leads to a reduced expression of pro-hematopoietic factors such as Scf, caused by increased H2AK119-ub1 and H3K27-me3 levels on the promoter region of these genes. On the other hand, the expression of myelopoiesis stimulating factors including Csf3 was increased by enriched H3K4-me3 and H3K27-ac levels on their promoter, causing myeloid skewing. Notably, loss of Bap1 substantially blocks B lymphopoiesis and skews the differentiation of hematopoietic precursors toward myeloid lineages in vitro, which is reversed by G-CSF neutralization. Thus, our study uncovers a key role for Bap1 expressed in endosteal MSCs in controlling normal hematopoiesis in mice by modulating expression of various niche factors governing lymphopoiesis and myelopoiesis via histone modifications.
2022-04-25 | GSE198823 | GEO
Project description:Hematopoiesis occurs within a unique bone marrow (BM) microenvironment which consists of various niche cells, cytokines, growth factors and extracellular matrix components. These multiple components directly or indirectly regulate the maintenance and differentiation of hematopoietic stem cells (HSCs). Here we report that Bap1 in BM mesenchymal stromal cells (MSCs) is critical for the maintenance of HSCs and B lymphopoiesis. Mice lacking Bap1 in MSCs show aberrant differentiation of hematopoietic stem and progenitor cells, impaired B lymphoid differentiation, and expansion of myeloid lineages. Mechanistically, Bap1 loss in distinct endosteal MSCs, expressing Prx1 but not Lepr, leads to aberrant expression of genes affiliated with BM niche functions. Bap1 deficiency leads to a reduced expression of pro-hematopoietic factors such as Scf, caused by increased H2AK119-ub1 and H3K27-me3 levels on the promoter region of these genes. On the other hand, the expression of myelopoiesis stimulating factors including Csf3 was increased by enriched H3K4-me3 and H3K27-ac levels on their promoter, causing myeloid skewing. Notably, loss of Bap1 substantially blocks B lymphopoiesis and skews the differentiation of hematopoietic precursors toward myeloid lineages in vitro, which is reversed by G-CSF neutralization. Thus, our study uncovers a key role for Bap1 expressed in endosteal MSCs in controlling normal hematopoiesis in mice by modulating expression of various niche factors governing lymphopoiesis and myelopoiesis via histone modifications.
2022-04-25 | GSE198649 | GEO