Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent progenitor cells
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ABSTRACT:
PROVIDER: PRJNA420373 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6330503_1.fastq.gz | Fastqsanger.gz | |||
| SRR6330503_2.fastq.gz | Fastqsanger.gz | |||
| SRR6330504_1.fastq.gz | Fastqsanger.gz | |||
| SRR6330504_2.fastq.gz | Fastqsanger.gz | |||
| SRR6330505_1.fastq.gz | Fastqsanger.gz |
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Project description:Here we report a transcriptomic analysis of fate-restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate-restricted retinal progenitor cells
2018-10-03 | GSE107498 | GEO
Project description:During development, multipotent retinal progenitor cells generate a large number of unique cell types. Recent evidence suggests that there are fate-restricted progenitor cell states in addition to multipotent ones. Here we report a transcriptomic analysis of fate- restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate- restricted retinal progenitor cells. This differential regulation occurs in chick and in a different restricted progenitor population in mouse suggesting that this is a conserved feature of progenitor dynamics during retinal development. S-phase labeling also revealed that nuclear positions of restricted progenitor populations occupy distinct spatial niches within the developing chick retina. Using a conserved regulatory element proximal to the VSX2 gene, a potential negative feedback mechanism from specific transcription factors enriched in cone/horizontal cell progenitor cells was identified. This study identifies conserved molecular and cellular changes that occur during the generation of fate restricted retinal progenitor cells from multipotent retinal progenitor cells.
| S-EPMC6441625 | biostudies-literature
Project description:The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133- positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+CD140a- cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133+CD140a- NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+CD140a+ cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133+CD140a- cells. As human CD133+ cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain. 12 samples, 4 groups (FACS-sorted cell populations),3 replicates in each group, each replicate is from a separate patient sample
2013-04-23 | E-GEOD-40676 | biostudies-arrayexpress
Project description:The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133- positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+CD140a- cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133+CD140a- NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+CD140a+ cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133+CD140a- cells. As human CD133+ cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain.
2013-04-23 | GSE40676 | GEO
Project description:3’-Seq of multipotent progenitor cells MPP5
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Project description:Here, we present a 3'-Seq dataset of ex vivo isolated mouse multipotent progenitor cells MPP5
2021-06-18 | E-MTAB-9135 | biostudies-arrayexpress
Project description:We compare the transcriptome of two different clones of multipotent adult progenitor cells (MAPCs) using Affymetrix arrays. Keywords: mRNA expression profiling, oligonucleotide microarrays, stem cells
2007-01-26 | GSE6291 | GEO
Project description:A unified workflow to define multipotent progenitor hierarchies
| PRJNA1107949 | ENA
Project description:Background: The vertebrate retina consists of six major classes of neuronal cells. During development, these cells are generated from a pool of multipotent retinal progenitor cells (RPCs) that express the gene Vsx2. Fate-restricted RPCs have recently been identified, with limited mitotic potential and cell fate possibilities compared to multipotent RPCs. One population of fate-restricted RPCs, marked by activity of the regulatory element ThrbCRM1, gives rise to both cone photoreceptors and horizontal cells. These cells do not express Vsx2, but co-express the transcription factors (TFs) Onecut1 and Otx2, which bind to ThrbCRM1. The components of the gene regulatory networks that control the transition from multipotent to fate-restricted gene expression are not known. This work aims to identify and evaluate cis-regulatory elements proximal to Onecut1 to identify the gene regulatory networks involved in RPC fate-restriction. Method: We identified regulatory elements through ATAC-seq and conservation, followed by reporter assays to screen for activity based on temporal and spatial criteria. The regulatory elements of interest were subject to deletion and mutation analysis to identify functional sequences and evaluated by quantitative flow cytometry assays. Finally, we combined the enhancer::reporter assays with candidate TF overexpression to evaluate the relationship between the TFs, the enhancers, and early vertebrate retinal development. Statistical tests included ANOVA, Kruskal-Wallis, or unpaired t-tests.Results: Two regulatory elements, ECR9 and ECR65, were identified to be active in ThrbCRM1(+) restricted RPCs. Candidate bHLH binding sites were identified as critical sequences in both elements. Overexpression of candidate bHLH TFs revealed specific enhancer-bHLH interactions. Nhlh1 overexpression expanded ECR65 activity into the Vsx2(+) RPC population, and overexpression of NeuroD1/NeuroG2/NeuroD4 had a similar effect on ECR9. Furthermore, bHLHs that were able to activate ectopic ECR9 reporter were able to induce endogenous Otx2 expression. Conclusions: This work reports a large-scale screen to identify spatiotemporally specific regulatory elements near the Onecut1 locus. These elements were used to identify distinct populations in the developing retina. In addition, fate-restricted regulatory elements responded differentially to bHLH factors, and suggest a role for retinal bHLHs upstream of the Otx2 and Onecut1 genes during the formation of restricted RPCs from multipotent RPCs.
2020-04-17 | GSE141019 | GEO
Project description:DNase-seq on 25 year old human male hematopoietic multipotent progenitor cell For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2016-12-07 | GSE90411 | GEO