ChIP-Seq analysis of PAX6A and PAX6D target genes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128134 | GEO | 2020/07/11
REPOSITORIES: GEO
Similar Datasets
Project description:PAX6 is essential for eye and forebrain development but how PAX6 instructs retinal versus neuroectoderm specification remains unknown. We found that the paired-less PAX6, PAX6D, is uniquely expressed in retinal cells during human eye development and along human embryonic stem cell (hESC) differentiation to retinal cells. HESCs with deletion of PAX6D failed to enter retinal differentiation. Induced expression of PAX6D but not PAX6A under the PAX6-null background restored the retinal differentiation capacity. ChIP-Seq, confirmed by functional assays, revealed a set of retinal genes and neural genes that are targets of PAX6D, including WNT8B. Inhibition of WNTs restored the retinal differentiation capacity of neuroepithelia with PAX6D knockout whereas activation of WNTs blocks retinal differentiation even when PAX6D is induced. Thus, PAX6D specifies neuroepithelia to retinal cells, partly via regulation of WNTs.
2020-07-11 | GSE128140 | GEO
Project description:The coupling between cell-cycle exit and onset of differentiation is a common feature throughout the developing nervous system, but the mechanisms that link these processes are mostly unknown. Although the transcription factor Pax6 was implicated in both proliferation and differentiation of multiple regions within the CNS, its contribution to the transition between these successive states remains elusive. To gain insight into the role of Pax6 during the transition from proliferating progenitors to differentiating precursors, we investigated cell-cycle and transcriptomic changes occurring in Pax6- retinal progenitor cells (RPCs). Our analyses revealed a unique cell-cycle phenotype of the Pax6-deficient RPCs, which included a reduced number of cells in the S phase, an increased number of cells exiting the cell cycle, and delayed differentiation kinetics of Pax6- precursors. These alterations were accompanied by co-expression of factors that promote (Ccnd1, Ccnd2, Ccnd3) and inhibit (P27kip1 and P27kip2) the cell cycle. Further characterization of the changes in transcription profile of the Pax6-deficient RPCs revealed abrogated expression of multiple factors which are known to be involved in regulating proliferation of RPCs, including the transcription factors Vsx2, Nr2e1, Plagl1 and Hedgehog signaling. These findings provide novel insight into the molecular mechanism mediating the pleiotropic activity of Pax6 in RPCs. The results further suggest that rather than conveying a linear effect on RPCs, such as promoting their proliferation and inhibiting their differentiation, Pax6 regulates multiple transcriptional networks which function simultaneously, thereby conferring the capacity to proliferate, assume multiple cell fates and execute the differentiation program into retinal lineages. The data contains 3 control and 3 Pax6 negative samples representing biological repeats. Each sample was prepared from ~1.8 million cells taken from the distal retina of either E12 alpha-Cre or Pax6 floxed alpha-Cre animals. Distally located retinal progenitors expressing Cre and eGFP were separated using FACS.
2013-08-01 | E-GEOD-45143 | biostudies-arrayexpress
Project description:During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, we aimed to determine the roles and the hierarchical organization of the PAX6-dependent gene regulatory network during the differentiation of the retinal pigmented epithelium (RPE). Somatic mutagenesis of Pax6 in the differentiating RPE revealed that PAX6 functions in a feed-forward regulatory loop with MITF during onset of melanogenesis. PAX6 both controls the expression of an RPE isoform of Mitf and synergizes with MITF to activate expression of genes involved in pigment biogenesis. This study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage. The data contains 3 control and 3 Pax6 negative samples representing biological repeats. Each sample was prepared from RPE dissected from E15.5 transgenic animals, either Pax6loxP/loxP or Pax6loxP/loxP;DctCre.
2014-04-08 | E-GEOD-56548 | biostudies-arrayexpress
Project description:During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, we aimed to determine the roles and the hierarchical organization of the PAX6-dependent gene regulatory network during the differentiation of the retinal pigmented epithelium (RPE). Somatic mutagenesis of Pax6 in the differentiating RPE revealed that PAX6 functions in a feed-forward regulatory loop with MITF during onset of melanogenesis. PAX6 both controls the expression of an RPE isoform of Mitf and synergizes with MITF to activate expression of genes involved in pigment biogenesis. This study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage.
2014-04-08 | GSE56548 | GEO
Project description:The purpose of this study was to examine global gene expression during the differentiation of human embryonic stem cells to more restricted neural progenitors. We developed an adherent differentiation protocol with completely defined media that produced 2 distinct classes of neuroepithelia based on timing, morphology and expression of known neural markers. The first stage of differentiation is undifferentiated human ES cells (hESCs). The second stage is aggregates of these hESCs after 6 days of separation from supportive mouse embryonic fibroblasts. The third stage is a primitive anterior neuroepithelia that arises after 10 days of differentiation and is marked by a columnar morphology, expression of Pax6 and anterior neural patterning genes. The fourth stage peaks at 17 days when cells form rosettes that resemble the neural tube and express the pan-neural marker Sox1.
2007-03-09 | E-SMDB-3806 | biostudies-arrayexpress
Project description:The purpose of this study was to examine global gene expression during the differentiation of human embryonic stem cells to more restricted neural progenitors. We developed an adherent differentiation protocol with completely defined media that produced 2 distinct classes of neuroepithelia based on timing, morphology and expression of known neural markers. The first stage of differentiation is undifferentiated human ES cells (hESCs). The second stage is aggregates of these hESCs after 6 days of separation from supportive mouse embryonic fibroblasts. The third stage is a primitive anterior neuroepithelia that arises after 10 days of differentiation and is marked by a columnar morphology, expression of Pax6 and anterior neural patterning genes. The fourth stage peaks at 17 days when cells form rosettes that resemble the neural tube and express the pan-neural marker Sox1. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Using regression correlation
2010-07-01 | E-GEOD-5609 | biostudies-arrayexpress
Project description:The coupling between cell-cycle exit and onset of differentiation is a common feature throughout the developing nervous system, but the mechanisms that link these processes are mostly unknown. Although the transcription factor Pax6 was implicated in both proliferation and differentiation of multiple regions within the CNS, its contribution to the transition between these successive states remains elusive. To gain insight into the role of Pax6 during the transition from proliferating progenitors to differentiating precursors, we investigated cell-cycle and transcriptomic changes occurring in Pax6- retinal progenitor cells (RPCs). Our analyses revealed a unique cell-cycle phenotype of the Pax6-deficient RPCs, which included a reduced number of cells in the S phase, an increased number of cells exiting the cell cycle, and delayed differentiation kinetics of Pax6- precursors. These alterations were accompanied by co-expression of factors that promote (Ccnd1, Ccnd2, Ccnd3) and inhibit (P27kip1 and P27kip2) the cell cycle. Further characterization of the changes in transcription profile of the Pax6-deficient RPCs revealed abrogated expression of multiple factors which are known to be involved in regulating proliferation of RPCs, including the transcription factors Vsx2, Nr2e1, Plagl1 and Hedgehog signaling. These findings provide novel insight into the molecular mechanism mediating the pleiotropic activity of Pax6 in RPCs. The results further suggest that rather than conveying a linear effect on RPCs, such as promoting their proliferation and inhibiting their differentiation, Pax6 regulates multiple transcriptional networks which function simultaneously, thereby conferring the capacity to proliferate, assume multiple cell fates and execute the differentiation program into retinal lineages.
2013-08-01 | GSE45143 | GEO
Project description:The purpose of this study was to examine global gene expression during the differentiation of human embryonic stem cells to more restricted neural progenitors. We developed an adherent differentiation protocol with completely defined media that produced 2 distinct classes of neuroepithelia based on timing, morphology and expression of known neural markers. The first stage of differentiation is undifferentiated human ES cells (hESCs). The second stage is aggregates of these hESCs after 6 days of separation from supportive mouse embryonic fibroblasts. The third stage is a primitive anterior neuroepithelia that arises after 10 days of differentiation and is marked by a columnar morphology, expression of Pax6 and anterior neural patterning genes. The fourth stage peaks at 17 days when cells form rosettes that resemble the neural tube and express the pan-neural marker Sox1. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2007-03-05 | GSE5609 | GEO
Project description:The pigmented portion of ciliary epithelium in the adult mammalian eye harbors mitotically quiescent retinal sphere cells, which are capable of self-renewal and differentiating into retinal neurons when assayed in vitro; however, very little is known about the molecular mechanism controlling the proliferation and differentiation of these adult retinal stem cells or their molecular resemblance to mutipotent stem/progenitor cells during early eye development. This experiment studies the gene expression of first passage and primary human and mouse retinal sphere cells. Experiment Overall Design: this experiment include 4 samples and 12 replicates
2008-06-12 | E-GEOD-3791 | biostudies-arrayexpress
Project description:Uveal coloboma is a congenital eye malformation caused by failure of the optic fissure to close in early human development. Despite significant progress in identifying genes whose regulation is important for executing this closure, mutations are detected in a minority of cases using known gene panels, implying additional genetic complexity. We show that the mouse Zfp503/Nlz2 gene is dynamically regulated in developing mouse eyes and that loss of its expression results in uveal coloboma. KO embryos exhibit altered expression patterns of several key transcription factors involved in eye development, including Otx2, Mitf, Pax6, Pax2, Vax1 and Vax2, resulting in reduced melanin pigmentation in the presumptive retinal pigment epithelium and its differentiation into a neural-retina-like lineage. From a large cohort of patients with exome sequencing records, only one patient with clinical diagnosis of retinal degeneration was identified carrying a pPresumed loss-of-function variants in the human ortholog, ZNF503. Although no disease-causing association was demonstrated, because of the retinal degeneration rather than of uveal coloboma phenotype, are rare and may be associated with retinal degeneration, rather than a uveal coloboma phenotype, suggesting it is tempting to speculate that a pleiotropic role of ZNF503 might have a pleiotropic role in ocular development and physiology
2022-11-16 | GSE180641 | GEO