Embryonic Stem cells (ESCs) can be differentiated into ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. In regular culture conditions, ESCs' self-renewal is maintained through molecules that inhibit spontaneous differentiation enabling long-term cellular expansion. This undifferentiating condition is characterized by multiple metastable states that fluctuate between self-renewal and differentiation balance. Here, we aim to characterize the high-pluripotent ESC metastate marked by the expression of Zscan4 through a supervised machine learning framework based on an ensemble of support vector machine (SVM) classifiers. Our study revealed a leukaemia inhibitor factor (Lif) dependent not-canonical pluripotency signature (AF067063, BC061212, Dub1, Eif1a, Gm12794, Gm13871, Gm4340, Gm4850, Tcstv1/3, and Zfp352), that specifically marks Zscan4 ESCs' fluctuation. This novel ESC metastate is enhanced by high-pluripotency culture conditions obtained through Extracellular signal Regulated-Kinase (ERK) and Glycogen synthase kinase-3 (Gsk-3) signaling inhibition (2i). Significantly, we reported that the conditional ablation of the novel ESC metastate marked by the expression of Gm12794 is required for ESCs self-renewal maintenance. In conclusion, we extend the comprehension of ESCs biology through the identification of a novel molecular signature associated to pluripotency programming.

Identification of a Novel Gene Signature of ES Cells Self-Renewal Fluctuation through System-Wide Analysis / Cerulo, L; Tagliaferri, D; Marotta, P; Zoppoli, P; Russo, F; Mazio, C; DE FELICE, Mario; Ceccarelli, M; Falco, Geppino. - In: PLOS ONE. - ISSN 1932-6203. - 9:1(2014). [10.1371/journal.pone.0083235]

Identification of a Novel Gene Signature of ES Cells Self-Renewal Fluctuation through System-Wide Analysis

Zoppoli P;DE FELICE, MARIO;Ceccarelli M;FALCO, Geppino
2014

Abstract

Embryonic Stem cells (ESCs) can be differentiated into ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. In regular culture conditions, ESCs' self-renewal is maintained through molecules that inhibit spontaneous differentiation enabling long-term cellular expansion. This undifferentiating condition is characterized by multiple metastable states that fluctuate between self-renewal and differentiation balance. Here, we aim to characterize the high-pluripotent ESC metastate marked by the expression of Zscan4 through a supervised machine learning framework based on an ensemble of support vector machine (SVM) classifiers. Our study revealed a leukaemia inhibitor factor (Lif) dependent not-canonical pluripotency signature (AF067063, BC061212, Dub1, Eif1a, Gm12794, Gm13871, Gm4340, Gm4850, Tcstv1/3, and Zfp352), that specifically marks Zscan4 ESCs' fluctuation. This novel ESC metastate is enhanced by high-pluripotency culture conditions obtained through Extracellular signal Regulated-Kinase (ERK) and Glycogen synthase kinase-3 (Gsk-3) signaling inhibition (2i). Significantly, we reported that the conditional ablation of the novel ESC metastate marked by the expression of Gm12794 is required for ESCs self-renewal maintenance. In conclusion, we extend the comprehension of ESCs biology through the identification of a novel molecular signature associated to pluripotency programming.
2014
Identification of a Novel Gene Signature of ES Cells Self-Renewal Fluctuation through System-Wide Analysis / Cerulo, L; Tagliaferri, D; Marotta, P; Zoppoli, P; Russo, F; Mazio, C; DE FELICE, Mario; Ceccarelli, M; Falco, Geppino. - In: PLOS ONE. - ISSN 1932-6203. - 9:1(2014). [10.1371/journal.pone.0083235]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/571940
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