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Transduction of human fibroblasts with Zic3 combined with OCT4, SOX2 and KLF4 induces stable neural progenitor cell lines

ABSTRACT: Lineage specific transcription factors (TF) define and reinforce tissue specific cell types. For instance, stable endoderm progenitors were established from human ESC by constitutive expression of SOX7 or SOX17. We hypothesized that combinatorial expression of OCT4, SOX2 and KLF4 together with the neural-lineage TF, Zic3, could directly convert fibroblasts into stable neuronal progenitor cells (NPC). Ensuing colonies predominantly expressed genes present in human NPC, as demonstrated by genome wide transcriptional analysis, and this phenotype could be maintained through many passages. When injected in immunodeficient mice, Zic3-induced (Zi)NPC form neuroendocrine tumors without evidence of mesoderm or endoderm. In vitro, ZiNPC spontaneously differentiated to neural cells only, and could be differentiated into astrocytes, oligodendrocytes and motor neuron lineages. In conclusion, addition of Zic3 during induced pluripotent stem cell (iPSC) generation, allows for the derivation of stable neural lineage progenitor cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE29770 | GEO | 2012/05/22

SECONDARY ACCESSION(S): PRJNA141041

REPOSITORIES: GEO

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Transduction of human fibroblasts with Zic3 combined with OCT4, SOX2 and KLF4 induces stable neural progenitor cell lines

Project description:Lineage specific transcription factors (TF) define and reinforce tissue specific cell types. For instance, stable endoderm progenitors were established from human ESC by constitutive expression of SOX7 or SOX17. We hypothesized that combinatorial expression of OCT4, SOX2 and KLF4M-BM- together with the neural-lineage TF, Zic3, could directly convert fibroblasts into stable neuronal progenitor cells (NPC). Ensuing colonies predominantly expressed genes present in human NPC, as demonstrated by genome wide transcriptional analysis, and this phenotype could be maintained through many passages.M-BM- When injected in immunodeficient mice, Zic3-induced (Zi)NPC form neuroendocrine tumors without evidence of mesoderm or endoderm. In vitro, ZiNPC spontaneously differentiated to neural cells only, and could be differentiated into astrocytes, oligodendrocytes and motor neuron lineages. In conclusion, addition of Zic3 during induced pluripotent stem cell (iPSC) generation, allows for the derivation of stable neural lineage progenitor cells. 3 hESC, 3 hESC-derived neurosphere and 3 ZiNPC samples were analyzed

2012-05-21 | E-GEOD-29770 | biostudies-arrayexpress

Transcription profiling by array of human embryonic stem cells over-expression SOX7 and SOX17

Project description:This study aimed to understand the transcriptional networks regulating endoderm specification from HESC and therefore explored the phenotype of CA1 and CA2 HESC constitutively over-expressing SOX7 or SOX17. Cell lines were created using an inducible construct whereby clonal populations containing transgene integration are selected by Neomycin resistance without expressing of the gene of interest (NoCre controls). Transgene expression is induced via Cre-mediated recombination and selected for puromycin resistance (SOX O/E). The phenotype of the resulting cells suggests that SOX7 expressing HESC represent stable extraembryonic endoderm progenitors, while SOX17 expressing HESC represent early definitive endoderm progenitors. Both in vitro and in vivo SOX7 expressing HESC are restricted to the extraembryonic endoderm lineage, while SOX17 expressing HESC demonstrate mesendodermal specificity. In vitro, SOX17 expressing HESC efficiently produce mature definitive endoderm derivatives. The molecular phenotype of the resulting SOX7 and SOX17 expressing HESC was characterized by microarray analysis Experiment Overall Design: Total RNA was extracted from confluent monolayer cultures of SOX7 over-expressing HESC, SOX17 over-expressing HESC, and their respective control parental HESC lines (designated NoCre Sox7 and NoCre Sox17).

2008-10-20 | E-GEOD-10809 | biostudies-arrayexpress

Zic3 interacts with distant regulatory elements to regulate zebrafish developmental genes

Project description:Zic3 regulates early embryonic patterning in vertebrates. Its loss-of-function disrupts gastrulation, left-right patterning, and neurogenesis. We use the zebrafish as a model to study the developmental role of Zic3 in vivo. Using a combination of two genomics approaches – ChIP-seq and microarray, we identified Zic3 targets, which include genes from the Nodal and Wnt pathways, and show for the first time cis-regulation of these genes by Zic3 using in vivo enhancer assay. We uncovered a previously unrecognized link between Zic3 and the non-canonical Wnt pathway in gastrulation and left-right patterning, and identified neural pre-pattern genes as Zic3 targets during the early steps of neural induction. Zic3 preferably binds to distal intergenic regions, some of which contain evolutionarily conserved functional enhancers. Our study establishes the zebrafish as an excellent model for genome-wide study of a transcription factor in vivo.

2014-02-27 | GSE41458 | GEO

Zic3 interacts with distant regulatory elements to regulate zebrafish developmental genes

2014-02-27 | E-GEOD-41458 | biostudies-arrayexpress

Global gene expression from SOX7 and SOX17 over-expressing human embryonic stem cells (CA1 and CA2 lines)

2008-08-11 | GSE10809 | GEO

Comparative analysis of gene expression in control and Zic3 knockdown mESCs differentiated to neurons

Project description:To determine the effct of Zic3 knockdown on the neural differentiation profile of mESCs

2024-01-05 | GSE221773 | GEO

ChIP-seq of Zic3 in ES-E14Tg2a embryonic stem cells after 2 days of differentiation to epiblast-like cells

Project description:Identification of Zic3 cistrome at ESC, d1EpiLC and d2EpiLC. ChIPmentaion experiments were performed using ZIC3 (Abcam, ab222124) antibody in the Rex1GFPd2 mouse embryonic stem cell line (ESC; parental line; E14Tg2a) and d1- and d2-EpiLC differentiated states.

2019-05-11 | E-MTAB-7208 | biostudies-arrayexpress

RNA-seq of E14Tg2a cells upon Zic3 knockdown after day1 and day2 of differentiation into epiblast-like stem cells

Project description:Identification of Zic3-dependent transcriptome at d1EpiLC and d2EpiLC. Gene expression was studied in the presence or absence of Zic3 (RNAi) in the Rex1GFPd2 mouse embryonic stem cell line (parental line; E14Tg2a) in d1- and d2-EpiLC differentiated states.

2019-05-11 | E-MTAB-7206 | biostudies-arrayexpress

Zic3 ChIP-on-chip in mouse ES cells

Project description:The transcription factor Zic3 is required for maintenance of embryonic stem (ES) cell pluripotency (Lim LS et al, Mol Biol Cell. 2007;18:1348-1358). By genome-wide chromatin immunoprecipitation (ChIP-chip) in ES cells, we have identified 379 direct Zic3 targets, many of which are functionally associated with pluripotency, cell cycle, proliferation, oncogenesis and early embryogenesis.

2010-09-13 | GSE22195 | GEO

PLURIPOTENCY REGULATOR ZIC3 IS AN EARLY LINEAGE SPECIFIER

Project description:Sustained expression of the key pluripotency transcriptional regulators and proliferative factors is needed for the maintenance of embryonic stem cells and early progenitors of various lineages. Zic3 is one of those factors which has been shown to be important for embryonic stem cell pluripotency. Through combinatorial analysis of transcription factor binding sites and the corresponding gene-regulation, we show that Zic3 not only activates key pluripotency genes but also acts cooperatively with them in connecting important circuits of regulation in ES cell in proliferation and maintenance of early progenitors.

2015-12-30 | GSE37889 | GEO

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