Recapitulative hematopoietic development of human pluripotent stem cells in the absence of exogenous cytokines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA670169 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We tested whether the sustained hematopoietic differentiation of hPSCs can be achieved in defined cell culture conditions without addition of hematopoietic cytokines. Here we show that the endogenous stimuli were sufficient to induce a robust generation of clonogenic hematopoietic progenitors, maturation of blood cells, emergence of the definitive cell lineages, and progenitors that were phenotypically identical to early human embryonic hematopoietic stem cells (HSCs). Our novel cytokine-free protocol is efficient, reproducible, and can be applied for hematopoietic differentiation of human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs). The removal of cytokines from the differentiation led to detecting a vast developmental potential of the early human blood cells. We also found that the cytokine-free hematopoietic differentiation of hPSCs is associated with strong activation of hPSC-derived inflammatory cells. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying early human hematopoietic development
2020-10-21 | GSE159672 | GEO
Project description:To improve the recapitulative quality of human pluripotent stem cell (hPSC) differentiation, we removed exogenous haematopoietic cytokines from the defined differentiation system. Here, we show that endogenous stimuli and VEGF are sufficient to induce robust hPSC-derived haematopoiesis, intensive generation of haematopoietic progenitors, maturation of blood cells and the emergence of definitive precursor cells including those that phenotypically identical to early human embryonic haematopoietic stem cells (HSCs). Moreover, the cytokine-free system produces significantly higher numbers of haematopoietic progenitors compared to the published protocols. The removal of cytokines revealed a broad developmental potential of the early blood cells, stabilized the hPSC-derived definitive precursors and led to spontaneous activation of inflammatory signalling. Our cytokine-free protocol is simple, efficient, reproducible and applicable for embryonic stem cells (ESCs) and induced PSCs. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying the early human haematopoietic development.
| S-EPMC8435420 | biostudies-literature
Project description:Long-term culture of human telencephalic organoids cultured in the presence or absence of exogenous ECM. To evaluate how ECM supplementation influences organoid development, we supplied exogenous ECM in the form of Matrigel at the beginning of neuroepithelialisation (day 10, D10), either as a solid droplet that provides long-term exposure to a polymerized network of ECM proteins (droplet embedding - condition "drop" in the metadata table), or transiently dissolved in the culture medium (concentration of 2%V/V ) from D10 to D13 (liquid embedding - "liq"). These protocols were compared to one without exposure to exogenous ECM ("no"). Organoids were processed at 120 days of culture, when mature cortical tissue is present.
2023-10-25 | GSE220085 | GEO
Project description:The variation among induced pluripotent stem cells (iPSCs) in their differentiation capacity to specific lineages is frequently attributed to somatic memory. In this study, we compared hematopoietic differentiation capacity of 35 human iPSC lines derived from four different tissues and four embryonic stem cell lines. The analysis revealed that hematopoietic commitment capacity (PSCs to hematopoietic precursors) is correlated with the expression level of the IGF2 gene independent of the iPSC origins. In contrast, maturation capacity (hematopoietic precursors to mature blood) is affected by iPSC origin; blood-derived iPSCs showed the highest capacity. However, some fibroblast-derived iPSCs showed higher capacity than blood-derived clones. Tracking of DNA methylation changes during reprogramming reveals that maturation capacity is highly associated with aberrant DNA methylation acquired during reprogramming, rather than the types of iPSC origins. These data demonstrated that variations in the hematopoietic differentiation capacity of iPSCs are not attributable to somatic memories of their origins. human pluripotent stem cell-derived hematopoietic precursor cells (n = 33)
2016-06-29 | E-GEOD-60810 | biostudies-arrayexpress
Project description:Human induced pluripotent stem (iPS) cells have previously been derived from somatic cells using viral vectors that integrate transgenes into the genome. Genomic integration, however, can allow persistent leaky expression of the transgenes and can create insertional mutations, thus limiting the utility of these cells for both research and clinical applications. Here, we describe the derivation of human iPS cells free of vector and transgene sequences using non-integrating oriP/EBNA1-based episomal vectors. The resulting iPS cells are similar to human embryonic stem (ES) cells in both proliferative and developmental potential. These results demonstrate that reprogramming of human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors, and removes one important obstacle to the clinical applications of these cells. This SuperSeries is composed of the following subset Series:; GSE15175: Human induced pluripotent stem cells free of exogenous DNA are derived with episomal vectors (fig 1.c); GSE15176: Human induced pluripotent stem cells free of exogenous DNA are derived with episomal vectors (fig 4.a) Experiment Overall Design: Total 21 samples were analyzed to confirm the similarity of human iPS cells derived with episomal vectors with human ES cells, and a dissimilarity with fibroblasts. Experiment Overall Design: Refer to individual Series
2009-04-04 | E-GEOD-15148 | biostudies-arrayexpress
Project description:Pluripotent stem cells (PSC) represent an alternative source of hematopoietic stem cells (HSCs). Clinical translation is impeded by limited engraftment of human (h)PSC-multipotent progenitor cells (MPP). This barrier suggests that additional cues are required for definitive hematopoiesis. We hypothesized that vascular niche producing Notch ligands Jagged-1 (JAG1) and Delta-like ligand-4 (DLL4) would drive definitive hematopoiesis. To test our hypothesis, hes2 human embryonic stem cells (hESC) 2 and Macaca nemestrina (Mn) iPSC line-7 were differentiated with cytokines ± endothelial cells (EC), which express JAG1 and DLL4. EC co-culture supported emergence of 8-fold more CD34+CD45+ cells compared to co-culture with cytokines ± ECs with JAG1 or DLL4 knockdown. EC-induced cells exhibit Notch activation and express HSC-specific targets of Notch signaling RUNX1 and GATA2. EC-induced PSC-MPP engraft at a higher level in NSG mice compared to cytokine-induced cells (10% >5 months), and selection increased engraftment (30%). Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction is similar to levels achieved for cord blood MPP and up to 20-fold higher than hPSC-MPP engraftment. Our findings identify a previously underappreciated role for endothelial Notch ligands in PSC definitive hematopoiesis and production of long-term engrafting CD34+ cells and suggest they are critical for HSC emergence. Transcriptome sequencing of Macaca nemestrina (Mn) iPSCs
2015-12-31 | E-GEOD-64644 | biostudies-arrayexpress
Project description:The variation among induced pluripotent stem cells (iPSCs) in their differentiation capacity to specific lineages is frequently attributed to somatic memory. In this study, we compared hematopoietic differentiation capacity of 35 human iPSC lines derived from four different tissues and four embryonic stem cell lines. The analysis revealed that hematopoietic commitment capacity (PSCs to hematopoietic precursors) is correlated with the expression level of the IGF2 gene independent of the iPSC origins. In contrast, maturation capacity (hematopoietic precursors to mature blood) is affected by iPSC origin; blood-derived iPSCs showed the highest capacity. However, some fibroblast-derived iPSCs showed higher capacity than blood-derived clones. Tracking of DNA methylation changes during reprogramming reveals that maturation capacity is highly associated with aberrant DNA methylation acquired during reprogramming, rather than the types of iPSC origins. These data demonstrated that variations in the hematopoietic differentiation capacity of iPSCs are not attributable to somatic memories of their origins. Undifferentiated human induced pluripotent stem cells (N = 23)
2016-06-29 | E-GEOD-60809 | biostudies-arrayexpress
Project description:Induced pluripotent stem cells hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained.
2013-07-26 | GSE49231 | GEO
Project description:Induced pluripotent stem cells hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained. We created and analyzed three separate iPSC clones from fibroblasts of three different normal individuals using a standardized approach that included excision of integrated reprogramming genes by Cre-Lox mediated recombination. Gene expression profiling and hematopoietic differentiation assays showed that independent lines from the same individual were generally more similar to each other than those from different individuals.
2013-07-26 | E-GEOD-49231 | biostudies-arrayexpress
