MicroRNAs Contribute to iPSC-Somatic Donor Memory
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE45219 | GEO | 2014/01/27
SECONDARY ACCESSION(S): PRJNA193226
REPOSITORIES: GEO
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Project description:miRNA expression analysis in iPSC derived from CD133+cells from Cord Blood We analyzed 1 array from CBiPS b- high passage numbers; 1 array from CBiPS b- low passage numbers; 2 array from CD133+celld from Cord Blood; 1 array from ES; 1 arrays from FiPS-high passage numbers
2014-01-27 | E-GEOD-45219 | biostudies-arrayexpress
Project description:Induced pluripotent stem cells (iPSCs) maintain during the first few culture passages a set of epigenetic marks and metabolites characteristic of their somatic cell of origin, a concept defined as epigenetic donor memory. These residual somatic features are lost over time after extensive culture passaging. Therefore, epigenetic donor memory may be responsible for the higher differentiation efficiency toward the tissue of origin observed in low passage iPSCs versus high passage iPSC or iPSCs derived from a different tissue source. Remarkably, there are no studies on the relevance of microRNA (miRNA) memory following reprogramming, despite the established role of these molecules in the context of pluripotency and differentiation. Using hematopoietic progenitors cells as a model, we demonstrated that miRNAs play a central role in somatic memory retention in iPSCs. Moreover, the comparison of the miRNA expression profiles among iPSCs from different sources allowed for the detection of a set of candidate miRNAs responsible for the higher differentiation efficiency rates toward blood progenitors observed in low passage iPSCs. Combining bioinformatic predictive algorithms with biological target validation, we identified miR-155 as a key player for the in vitro differentiation of iPSC toward hematopoietic progenitors. In summary, this study reveals that during the initial passages following reprogramming, iPSCs maintained the expression of a miRNA set exclusive to the original somatic population. Hence the use of these miRNAs might hold a direct application toward our understanding of the differentiation process of iPSCs toward hematopoietic progenitor cells.
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Project description:Several studies have discussed the possibility that donor cell type may influence the epigenetics and differentiation potential of iPSCs, but it remains unclear whether iPS cells derived from different tissue sources reserve their epigenetic memory. Here, we clarify that iPSCs obtained from different tissues exhibit specific epigenetic patterns. We determined the DNA methylation profiles of 12 human cell lines, including 3 adult fibroblast cell-derived iPSC lines, 2 peripheral blood-derived mononuclear cell(PBMC)-derived iPSC lines, 2 amniotic cell-derived iPSC lines and the 5 corresponding parent cell lines. We found that the catalog of tissue-specific DNA methylation was preserved in the iPSC line as epigenetic memory during reprogramming.
2016-05-02 | GSE80969 | GEO
Project description:Global gene expression analysis of (a) human embryonic stem cells, (b) low passage episomal stromal-primed iPSC derived from growth-factor activated CD34+ myeloid progenitors from cord blood or GCSF mobilized peripheral blood, and (d) samples of donor fibroblasts or myeloid progenitors
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Project description:Global microRNA analysis of (a) human embryonic stem cells, (b) low passage episomal stromal-primed myeloid iPSC, (c) intermediate passage fibroblast iPSC, and (d) samples of corresponding donor cells.
2017-12-31 | GSE44423 | GEO
Project description:Documents of DNA expression of 4 human induced pluripotent stem cell (iPSC) lines from umbilical cord mesenchymal cells (UMCs) and amniotic mesenchymal cells (AMCs). We used microarrays to identify similarity between 4 iPSC cell lines and the human embryonic stem cell (ESC) line H9. 2 AMC iPSC cell lines, 2 UMC iPSC cell lines, H9 ESC cell line. TRIZOL cell lysates were prepared.
2010-11-10 | E-GEOD-20581 | biostudies-arrayexpress
Project description:Transcription factor-mediated reprogramming yields induced pluripotent stem cells (iPSC) by erasing tissue specific methylation and re-setting DNA methylation status to an embryonic stage. We compared bona fide human iPSC derived from umbilical cord blood (CB) and neonatal keratinocytes (K). Through both incomplete erasure of tissue specific methylation and de novo tissue specific methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles. Functionally, CB-iPSC displayed better blood formation in vitro, whereas K-iPSC differentiated better to a keratinocyte fate, implying that the tissue of origin needs to be considered in future therapeutic applications of human iPSCs. We performed gene expression and global DNA methylation profiling on iPS and the source somatic cell types to search for evidence of epigenetic memory. We performed gene expression profiling to identify genes differentially expressed between keratinocytes and cord blood, and from induced pluripotent stem cells from these somatic tissues.
2011-11-29 | E-GEOD-27186 | biostudies-arrayexpress
Project description:Epigenetic memory in induced pluripotent stem cells (iPSCs), with regards to their somatic cell type of origin, might lead to variations in their differentiation capacities. In this context, iPSCs from human CD34+ hematopoietic stem cells (HSCs) might be more suitable for hematopoietic differentiation than commonly used fibroblast-derived iPSCs. To investigate the influence of an epigenetic memory on the ex vivo expansion of iPSCs into erythroid cells, we compared iPSCs from human neural stem cells (NSCs) and human cord blood-derived CD34+ HSCs and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells (RBCs). Although genome-wide DNA methylation profiling at all promoter regions demonstrates an epigenetic memory of iPSCs with regards to their somatic cell type of origin, we found a similar hematopoietic induction potential and erythroid differentiation pattern. All human iPSC lines showed terminal maturation into normoblasts and enucleated RBCs, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the CD34+ HSC-derived iPSCs. More detailed methylation analysis of the hematopoietic and erythrocyte promoters identified similar CpG methylation levels in the CD34+ iPSCs and NSC iPSCs, which confirms their comparable erythroid differentiation potential. To investigate the influence of an epigenetic memory on the ex vivo expansion of iPSCs into erythroid cells, we compared iPSCs from human neural stem cells (NSCs) and human cord blood-derived CD34+ HSCs and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells (RBCs). RNA samples for microarray analysis were prepared using RNeasy columns (Qiagen, Germany) with on-column DNA digestion. 300ng of total RNA per sample was used as the input in the linear amplification protocol (Ambion), which involved the synthesis of T7-linked double-stranded cDNAs and 12hrs of in vitro transcription incorporating the biotin-labeled nucleotides. Purified and labeled cRNA was then hybridized for 18hrs onto HumanHT-12 v4 expression BeadChips (Illumina, USA) following the manufacturer's instructions. After the recommended washing, the chips were stained with streptavidin-Cy3 (GE Healthcare) and scanned using the iScan reader (Illumina) and the accompanying software. The samples were exclusively hybridized as biological replicates. 8 samples were analyzed: CD34 1, Human CD34+ Cord blood CD34+ Hematopoyetic Stem Cell(HSC) population 1, 1 replicate CD34 2, Human CD34+ Cord blood CD34+ Hematopoyetic Stem Cell(HSC) population 2, 1 replicate CD34 OSiPS 1, Human Human two factors (POU5F1, SOX2) induced Pluripotent Cell (iPSC) reprogrammed from CD34+ Cord blood CD34+ Hematopoyetic Stem Cell(HSC) induced Pluripotent Cell (iPSC) population 1, 1 replicate CD34 OSKMiPS 1, Human Human four factors (POU5F1, SOX2, KLF4, CMYC) induced Pluripotent Cell (iPSC) reprogrammed from CD34+ Cord blood CD34+ Hematopoyetic Stem Cell(HSC) induced Pluripotent Cell (iPSC) population 1, 1 replicate CD34 OSiPS 2, Human Human two factors (POU5F1, SOX2) induced Pluripotent Cell (iPSC) reprogrammed from CD34+ Cord blood CD34+ Hematopoyetic Stem Cell(HSC) induced Pluripotent Cell (iPSC) population 2, 1 replicate CD34 OSKMiPS 2, Human Human four factors (POU5F1, SOX2, KLF4, CMYC) induced Pluripotent Cell (iPSC) reprogrammed from CD34+ Cord blood CD34+ Hematopoyetic Stem Cell(HSC) induced Pluripotent Cell (iPSC) population 2, 1 replicate H1, Human H1 embryonic stem cell (ESC), 1 replicate H9, Human H9 embryonic stem cell (ESC), 1 replicate
2015-02-20 | E-GEOD-55109 | biostudies-arrayexpress
Project description:Global gene expression analysis of (a) human embryonic stem cells, (b) low passage episomal stromal-primed myeloid iPSC, (c) intermediate passage fibroblast iPSC, and (d) samples of corresponding donor cells.
2016-09-13 | GSE44421 | GEO
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.
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