Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Cell cycle positioning drives heterogeneity within the pluripotent stem cell compartment

ABSTRACT: Heterogeneity in pluripotent cells marks a metastable state where cells may drift between native and lineage-primed populations. While the role for these heterogeneities are unclear, they may reflect the dynamic equilibriums of signaling networks and have a direct effect on differentiation potentialities. Here, we report the role of the cell cycle in establishing heterogeneity of human pluripotent stem cells. By utilizing the FUCCI cell cycle indicator system coupled to fluorescent activated cell sorting (FACS), we have uncovered that the cell cycle drives heterogeneity at the epigenetic, transcriptional and post-transcriptional levels. Our data show widespread dynamics in 5-hydroxymethylcytosine (5hmC) during the cell cycle. Furthermore, transcript profiling by RNA-sequencing identified >500 genes that were cell cycle-regulated, of which the largest cohort of genes were transcriptional regulators. In sum, we demonstrate the role of the cell cycle in coordinating cellular transitions between metastable states in pluripotent stem cells. mRNA sequencing of the cell cycle phases; early & late G1, S and G2/S from human ES cells in triplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Stephen Dalton 

PROVIDER: E-GEOD-53481 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cell-cycle control of developmentally regulated transcription factors accounts for heterogeneity in human pluripotent cells.

Singh Amar M AM   Chappell James J   Trost Robert R   Lin Li L   Wang Tao T   Tang Jie J   Matlock Brittany K BK   Weller Kevin P KP   Wu Hao H   Zhao Shaying S   Jin Peng P   Dalton Stephen S  

Stem cell reports 20131205 6

Heterogeneity within pluripotent stem cell (PSC) populations is indicative of dynamic changes that occur when cells drift between different states. Although the role of metastability in PSCs is unclear, it appears to reflect heterogeneity in cell signaling. Using the Fucci cell-cycle indicator system, we show that elevated expression of developmental regulators in G1 is a major determinant of heterogeneity in human embryonic stem cells. Although signaling pathways remain active throughout the ce  ...[more]

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