Gene expression of human chord blood hematopoietic progenitor cells and induced hemato-endothelial progenitor cells derived from human iPSC
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PROVIDER: PRJNA588969 | ENA |
REPOSITORIES: ENA
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Project description:Induced pluripotent stem cells (iPSC) offer a promising platform to model early embryonic developmental processes, to create disease models and proof-of-concept experiments for regenerative medicine. However, generation of iPSC derived hemato-endothelial and hematopoietic progenitor cells for these applications is challenging due to variable and limited cell numbers, which necessitates enormous up-scaling or development of demanding protocols. Here, we unravel the function of key transcriptional regulators SCL, LMO2, GATA2, ETV2 (SLGE) on early hemato-endothelial specification and establish a fully inducible and stepwise hemato-endothelial forward programming system, based on SLGE regulated overexpression. Regulated induction of SLGE in stable SLGE-iPSC lines drives very efficient generation of large numbers of hemato-endothelial progenitor cells (HEP) (CD144+/CD73-), which generate hematopoietic progenitor cells (CD45+/CD34+/CD38-/CD45RA-/CD90+/CD49f+) through a gradual process of endothelial-to-hematopoietic transition (EHT).
2019-11-13 | GSE140221 | GEO
Project description:Gene expression profile of human iPSC-derived nephron progenitor cells
| PRJNA486586 | ENA
Project description:Purpose: We designed this study to evaluate the feasibility of using only one factor to respecify human induced pluripotent stem cells (iPSCs)-derived blood cells into long-term engraftable hematopoietic stem and progenitor cells (HSPCs). We also parallelly compared iPSC-derived HSPCs (iHSPCs) with primary HSPCs under the same induction and transplantation condition in order to examine the functional equivalency between iHSPCs and bona fide HSPCs. Methods: In vitro derived human iPSC-HSPCs are induced with or without (w/o) doxycycline for the expression of MLL-AF4. In vivo derived bone marrow cells are harvested and FACS-sorted for human populations from primary transplants over nine to sixteen weeks after transplantation. Either iPSC-HSPCs or primary HSPCs, both of which are induced by MLL-AF4, is used for the transplantation experiments. iPSCs are either derived from peripheral blood mobilized CD34+ HSPCs (CD34-iPSC) or mononuclear cells (MN-iPSCs). Normal human CD34+ HSPCs and mononuclear cells are set as control groups. Results: MLL-AF4 can impart HSC and lymphoid potential to iPSC-derived blood cells in vitro, and induction of MLL-AF4 leads to the cellular identity transition from common myeloid progenitors to hematopoietic stem and progenitor cells. MLL-AF4 alone is sufficient to realize the potent engraftment of induced HSPCs (iHSPCs) from iPSCs, and multilineage and long-term hematopoiesis could be observed. Primary HSPCs with the induction of MLL-AF4 could gain significantly enhanced engraftability. During the long-term engraftment period, leukemic mutations with a bias to B-cell leukemia could be found in the iHSPCs and their derivatives. By contrast, MLL-AF4 induced primary HSPCs maintain the normal hematopoiesis without leukemic transformation. Conclusions: Our study has demonstrated for the first time, to our knowledge, that the pluripotency-dependent conversion of somatic cells to long-term engraftable HSPCs can be achieved by using a single factor in a non-integrative way. This study also suggests that iPSC-derived HSPCs are more prone to leukemic mutations during the long-term engraftment period, which provides a necessary caveat of using them in the actual therapies.
2018-01-31 | GSE103420 | GEO
Project description:We investigated the enriched miRNAs in exosomes from cardiac progenitor cells (CPCs) which were induced by a small molecule-ISX-9 compared with exosomes from human iPSC, embryoid bodies and commerical cardiac progenitor cells.
2019-02-12 | GSE126347 | GEO
Project description:We performed a microarray experiment to analyze the transcriptional profile of CHARGE patient iPSC-derived neural stem/progenitor cells to identify CHD7 target genes.
2018-03-28 | GSE108170 | GEO
Project description:Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells may inevitably contain tumorigenic or inappropriate cells. Purification of neural progenitor cells or DA neurons as suitable donor cells has been attempted, but the isolation of DA progenitor cells derived from human pluripotent stem cells has so far been unsuccessful. Here we show human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, Corin. we were able to develop a method for 1) scalable DA neuron induction on human laminin fragment and 2) sorting DA progenitor cells using an anti-Corin antibody. Furthermore, we determined the optimal timing for the cell sorting and transplantation. The grafted cells survived well and functioned as midbrain DA neurons in the 6-OHDA-lesioned rats, and showed minimal risk of tumor formation. The sorting of Corin-positive cells is favorable in terms of both safety and efficiency, and our protocol will contribute to the clinical application of human iPSCs for Parkinson’s disease. Differentiated human iPSC-derived neural progenitors just after sorting (day12 unsorted, day12 Corin+) and dopaminergic progenitors after an aggregation culture (day28 and day42, unsorted and day12-sorted, respectively), and human fetal ventral mesencephalon and dorsal mesencephalon (gestational age of 7.5 weeks) were subjected to RNA extraction and hybrdization on Affymetrix microarrays. Each sample except for human mesencephalon, undifferentiated iPSC, and day12-unsorted, day42-sample has 3 or 4 repeats.
2014-03-07 | E-GEOD-51214 | biostudies-arrayexpress
Project description:Human fetal lung tip progenitor cells
| PRJNA784950 | ENA
Project description:Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, tumorigenicity and immunogenicity are major obstacles to translational use. Here we demonstrate epidural therapeutics of human iPSC-NPC grafts after experimental ischemic stroke to avoid surgical damage and intracerebral teratomas. We found that human iPSC-NPCs co-cultured trans-membranously with rat cortical cells subjected to oxygen-glucose deprivation, compared with human mesenchymal stem cells from bone marrow and umbilical cord Wharton's jelly, superiorly enhanced neural survival and growth as well as mitigated astrogliosis. Using comparative whole-genome microarrays and cytokine arrays, we identified a neurorestorative secretome from iPSC-NPCs and neutralization of the enriched cytokines potently abolished the neuroprotective effects in the iPSC-NPC co-cultures. Moreover, we implanted the human iPSC-NPCs epidurally using fibrin glue over the peri-infarct cortex at 7 days following permanent middle cerebral artery occlusion in adult rats. The cell-treated rats showed significant improvement in their paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards compared to the vehicle-treated rats, accompanied by ameliorated infarct/atrophy volumes, inflammatory infiltration and astrogliosis, as well as augmented angiogenesis, oligodendrocyte precursor cells and white matter integrity. Some iPSC-NPCs migrated into the peri-infarct cortex but poorly survived by 21 dpt. This proof-of-concept study demonstrates that a less invasive yet effective epidural delivery route of human iPSC-NPCs may promote functional remodeling of the peri-infarct brain predominantly through distinct paracrine effects. cDNA samples from iPSC-NPC were hybridized to the human genome U133 Plus 2.0 GeneChip arrays.
2016-06-02 | E-GEOD-82101 | biostudies-arrayexpress
Project description:Embryonic stem cells are pluripotent and possess the ability to differentiate into numerous lineages during the developmental process. In similarity to embryonic stem cells, human induced pluripotent stem cells (iPSCs) possess the potential to differentiate into multiple lineages making them an excellent research tool. We generated iPSCs from multiple donors and also differentiated iPSCs from these donors into human neural stem/progenitor cells (NSCs). We used human transcriptome arrays to detail the programme of gene expression underlying NPC induction and identified distinct classes of up-regulated genes during this process. Human induced pluripotent stem cells (iPSCs) can be used to create neurons in vitro. This microarray allows researchers to check the expression of their gene of interest in iPSC-derived neurons and compare the gene expression profile of iPSC-derived neurons to other cell types or primary human tissue.
2014-09-12 | GSE61358 | GEO
Project description:During development, nephron progenitor forming one million nephrons, a functional unit in the kidney. However, nephron progenitor ceases before birth in human when they terminally differentiated to the nephron. Our lab established the method for induction of nephron progenitors from mouse Embryonic Stem (ES) cells and/or human induced Pluripotent Stem Cells (iPSCs) (Taguchi et al., Cell Stem Cell. 2014, 2017). For application of induced nephron progenitors to regenerative medicine, a large number of cells are required such as disease modeling and drug screening. To selectively propagate human iPS-derived nephron progenitors in vitro in an undifferentiated state, we developed SIX2-GFP iPS line and optimized culture condition of induced nephron progenitors by modifying our previously developed condition (Tanigawa et al., Cell Rep. 2016). To understand how whole gene expression profiles of human iPS-derived nephron progenitor cells are changed during culture, we isolated nephron progenitor cells by FACS and cultured in our defined culture condition. Purified RNAs from cultured cells at day 7 or un-cultured nephron progenitor cells were analyzed by RNA-seq.
2019-08-01 | GSE118729 | GEO