ArticleStem cell research & therapy2018
Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 23 citations in OpenAlex.
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- A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression.Nature communications · 2021Article
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- Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells.Scientific reports · 2020Article
- Selected Ionotropic Receptors and Voltage-Gated Ion Channels: More Functional Competence for Human Induced Pluripotent Stem Cell (iPSC)-Derived Nociceptors.Brain sciences · 2020Article
- Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization.International journal of molecular sciences · 2019Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDifferentiation of human induced pluripotent stem cells (hiPSCs) into retinal lineages offers great potential for medical application. Therefore, it is of crucial importance to know the key intrinsic regulators of differentiation and the specific biomarker signatures of cell lineages.
methodsIn this study, we used microarrays to analyze transcriptomes of terminally differentiated retinal ganglion cell (RGC) and retinal pigment epithelium (RPE) lineages, as well as intermediate retinal progenitor cells of optic vesicles (OVs) derived from hiPSCs. In our analysis, we specifically focused on the classes of transcripts that encode intrinsic regulators of gene expression: the transcription factors (TFs) and epigenetic chromatin state regulators. We applied two criteria for the selection of potentially important regulators and markers: firstly, the magnitude of fold-change of upregulation; secondly, the contrasted pattern of differential expression between OV, RGC and RPE lineages.
resultsWe found that among the most highly overexpressed TF-encoding genes in the OV/RGC lineage were three members of the Collier/Olfactory-1/Early B-cell family: EBF1, EBF2 and EBF3. Knockdown of EBF1 led to significant impairment of differentiation of hiPSCs into RGCs. EBF1 was shown to act upstream of ISL1 and BRN3A, the well-characterized regulators of RGC lineage specification. TF-encoding genes DLX1, DLX2 and INSM1 were the most highly overexpressed genes in the OVs, indicating their important role in the early stages of retinal differentiation. Along with MITF, the two paralogs, BHLHE41 and BHLHE40, were the most robust TF markers of RPE cells. The markedly contrasted expression of ACTL6B, encoding the component of chromatin remodeling complex SWI/SNF, discriminated hiPSC-derived OV/RGC and RPE lineages.
conclusionsWe identified novel, potentially important intrinsic regulators of RGC and RPE cell lineage specification in the process of differentiation from hiPSCs. We demonstrated the crucial role played by EBF1 in differentiation of RGCs. We identified intrinsic regulator biomarker signatures of these two retinal cell types that can be applied with high confidence to confirm the cell lineage identities.
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