Forced expression of four transcription factors Oct4,Sox2, Klf4 and Myc (OSKM) induces somatic cell reprogramming towards pluripotency. Major efforts have been made to characterize the molecular events involved in this process. Yet, it remains elusive how gene expression change, epigenetic landscape remodelling and cell fate conversion are triggered by expression of these Yamanaka factors. To address this gap, we utilized a secondary inducible reprogramming system and performed genome-wide profilings of Oct4 binding, histone modification (H3K4me3/H3K27me3/H3K4me1/H3K27ac), and gene expression analysis during this process. Through integrative analysis, we revealed stage-specific Oct4 binding and enhancer signatures in consistence with gene expression changes, in which the initial regression of somatic program is followed by the gradual acquisition of pluripotent program. Oct4 preferatially binds to H3K4me1 marked enhancer regions and Oct4 binding is positively correlated with active mark H3K27ac. Moreover, we observed significant enhancer activation of epigenetic related genes, especially acetylation associated genes, prior to pluripotency network activation, suggesting a pivotal role of epigenetic remodelling in the process of pluripotency acquisition and maintenance.
Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming.
Specimen part
View SamplesDetection of gene expression profiles during OT(Oct4+Tet1)-mediated iPSC induction and demonstration the pluripotency of OT-iPSC.
No associated publication
Specimen part, Treatment
View SamplesIn the early zebrafish embryo, the developing genome profile can be interfered with by exposure to pentachlorophenol, and some specific sets of genes are up-regulated or down-regulated. We used microarrays to detail the global program of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage.
Specimen part, Treatment
View SamplesThe direct conversion, or trans-differentiation, of non-cardiac cells into cardiomyocytes by forced expression of transcription factors and microRNAs provide promising ways of cardiac regeneration. However, genetic manipulations are still not desirable in real clinical applications. we report the generation of automatically beating cardiomyocyte-like cells from mouse fibroblasts with only chemical cocktails. These chemical-induced cardiomyocyte-like cells (CiCMs) express cardiomyocyte-specific markers, exhibit sarcomeric organization, and possess typical cardiac calcium flux and electrophysiological features. Microarray-bassed gene expression patterns of Mouse embryonic fibroblasts (MEFs), CiCMs, and cardiomyocytes(CMs) indicated a clear transition from dividing MEFs to differentiated cardiomyocyte-like state in CiCM samples.
Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails.
Specimen part
View SamplesNeural crest defects lead to congenital heart disease involving outflow tract (OFT) malformation. Integrin-linked-Kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in neural crest cells (NCC), but its role in NCC and OFT morphogenesis remains unknown.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Cell line
View SamplesSin3a, a known master scaffold, provides unique contact surfaces for interaction with particular accessory proteins to repress the transcription of specific genes. Surprisingly, our results also suggest that Sin3a has a role in transcriptional activation.
Sin3a-Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency.
Specimen part, Cell line
View SamplesWhile the functional roles of long non-coding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naive state of embryonic stem cells (ESCs) are known. Here, we report a naive-state-associated lncRNA, lincU, which is intrinsically activated by NANOG in naive mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from naive state to primed state, whereas ectopic lincU expression maintains mESCs in the naive state. Mechanistically, we demonstrate that lincU directly binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naive state. Importantly, we reveal the functional role of lincU to be evolutionarily conserved in human. Our findings thus unveil lincU as a conserved lncRNA that intrinsically restricts MAPK/ERK activity and maintains the naive state of ESCs.
No associated publication
Cell line
View SamplesLittle is known about the roles of Rictor/mTORC2 in the leukemogenesis of AML. Here, we demonstrated that Rictor is essential for the maintenance of MLL-driven leukemia by preventing LSCs from exhaustion. Rictor depletion led to a reactive activation of mTORC1 signaling by facilitating the assembly of mTORC1. Hyperactivated mTORC1 signaling in turn drove LSCs into cycling, compromised the quiescence of LSCs and eventually exhausted their capacity to generate leukemia.
Rictor has a pivotal role in maintaining quiescence as well as stemness of leukemia stem cells in MLL-driven leukemia.
Specimen part
View Samples