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Human embryonic stem cells (hESCs) are derived from the inner cell mass of the blastocyst. Despite sharing the common property of pluripotency, hESCs are notably distinct from epiblast cells of the preimplantation blastocyst. Here we use a combination of three small-molecule inhibitors to sustain hESCs in a LIF signaling-dependent hESC state (3iL hESCs)… (More)
The maintenance of mouse embryonic stem cells (mESCs) requires LIF and serum. However, a pluripotent "ground state," bearing resemblance to preimplantation mouse epiblasts, can be established through dual inhibition (2i) of both prodifferentiation Mek/Erk and Gsk3/Tcf3 pathways. While Gsk3 inhibition has been attributed to the transcriptional derepression… (More)
During differentiation, human embryonic stem cells (hESCs) shut down the regulatory network conferring pluripotency in a process we designated pluripotent state dissolution (PSD). In a high-throughput RNAi screen using an inclusive set of differentiation conditions, we identify centrally important and context-dependent processes regulating PSD in hESCs,… (More)
The cellular identity of both pluripotent and differentiated cells is defined by the concerted interplay of transcriptional factors as well as other modulators such as epigenetic and signaling mediators. Therefore, the manipulation of a cell's transcriptional network directly facilitates inter-conversion between cellular identities. Understanding the… (More)
The forkhead box O (FoxO) family is involved in diverse cellular processes such as tumor suppression, stress response, and metabolism. In a recent Nature Cell Biology Letter, Zhang et al. (2011) uncover a novel role for FoxO proteins in regulating the identity of human ESCs.
The cyclic AMP-Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved signal transduction mechanism that regulates cellular growth and differentiation in animals and fungi. We present a mathematical model that recapitulates the short-term and long-term dynamics of this pathway in the budding yeast, Saccharomyces cerevisiae. Our model is aimed at… (More)
Genome architecture is associated with cellular identity, but how this organization changes during reprogramming is not well understood. Now in Cell Stem Cell, Krijger et al. (2016) and Beagan et al. (2016) report 3D chromatin interaction maps before and after reprogramming, providing evidence for topological memory in induced pluripotent stem cells.
While distinct cell cycle structures have been known to correlate with pluripotent or differentiated cell states , there is no evidence on how the cell cycle machinery directly contributes to human embryonic stem cell (hESC) pluripotency. We established a determinant role of cell cycle machineries on the pluripotent state by demonstrating that the… (More)
The identity of a cell is determined by the concerted interplay of multiple molecular modulators such as transcription factors, chromatin modifiers and signalling mediators. Among these, the transcriptional circuitry holds great influence on the specification and maintenance of a cellular state, and its perturbation can trigger a transition to another cell… (More)
The repertoire of transcripts encoded by the genome contributes to the diversity of cellular states. Functional genomics aims to comprehensively uncover the roles of these transcripts to reconstruct biological networks and transform this information into useful knowledge. High-throughput functional screening has served as a powerful genetic discovery tool… (More)