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E-GEOD-45143 - Pax6 is required for normal cell cycle exit and the differentiation kinetics of retinal progenitor cells

Status
Released on 1 August 2013, last updated on 2 June 2014
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (7)
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.
Experiment type
transcription profiling by array 
Contacts
Chen Farhy <geo@ncbi.nlm.nih.gov>, Micael Elgart, Ruth Asher-Padan, Varda Oron-Karni, Yotam Menuchin
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-45143.idf.txt
Sample and data relationshipE-GEOD-45143.sdrf.txt
Raw data (1)E-GEOD-45143.raw.1.zip
Processed data (1)E-GEOD-45143.processed.1.zip
Array designA-AFFY-45.adf.txt
Links