Author
Qiang Wu
Other affiliations: Macau University of Science and Technology, Genome Institute of Singapore
Bio: Qiang Wu is an academic researcher from National University of Singapore. The author has contributed to research in topics: Embryonic stem cell & Homeobox protein NANOG. The author has an hindex of 13, co-authored 20 publications receiving 4987 citations. Previous affiliations of Qiang Wu include Macau University of Science and Technology & Genome Institute of Singapore.
Papers
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TL;DR: By integrating RNA interference–mediated depletion of Oct4 and Nanog with microarray expression profiling, it is demonstrated that these factors can activate or suppress transcription, and it is shown that common core downstream targets are important to keep ES cells from differentiating.
Abstract: Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse ES cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis-acting elements mediating their respective binding to genomic sites. By integrating RNA interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep ES cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.
2,489 citations
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TL;DR: A robust approach is described that couples chromatin immunoprecipitation (ChIP) with the paired-end ditag (PET) sequencing strategy for unbiased and precise global localization of transcription-factor binding sites (TFBS).
1,180 citations
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TL;DR: It is demonstrated that Sall4 is a transcriptional activator of Pou5f1 and has a critical role in the maintenance of ES cell pluripotency by modulating Oct4 expression, and indicates that SAll4 is important for early embryonic cell-fate decisions.
Abstract: Embryonic stem (ES) cells are pluripotent cells that can self-renew or differentiate into many cell types. A unique network of transcription factors and signalling molecules are essential for maintaining this capability. Here, we report that a spalt family member, Sall4, is required for the pluripotency of ES cells. Similarly to Oct4, a reduction in Sall4 levels in mouse ES cells results in respecification, under the appropriate culture conditions, of ES cells to the trophoblast lineage. Sall4 regulates transcription of Pou5f1 which encodes Oct4. Sall4 binds to the highly conserved regulatory region of the Pou5f1 distal enhancer and activates Pou5f1 expression in vivo and in vitro. Microinjection of Sall4 small interfering (si) RNA into mouse zygotes resulted in reduction of Sall4 and Oct4 mRNAs in preimplantation embryos and significant expansion of Cdx2 expression into the inner cell mass. These results demonstrate that Sall4 is a transcriptional activator of Pou5f1 and has a critical role in the maintenance of ES cell pluripotency by modulating Oct4 expression. The data also indicates that Sall4 is important for early embryonic cell-fate decisions.
557 citations
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TL;DR: It is suggested that Sall4 and Nanog form a regulatory circuit similar to that of Oct4 and Sox2, which encode for key transcription factors in ES cells by cooperating with Nanog.
321 citations
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TL;DR: This article showed that p53 also regulates osteoblast differentiation, bone formation, and osteoclast-dependent osteogenesis, as a result of an increase in expression of osterix.
Abstract: p53 is a well known tumor suppressor. We show that p53 also regulates osteoblast
differentiation, bone formation, and osteoblast-dependent osteoclast differentiation.
Indeed,
p53 − / − mice display a high bone mass phenotype, and
p53 − / − osteoblasts show accelerated differentiation, secondary to an increase in expression of
the osteoblast differentiation factor osterix, as a result. Reporter assays indicate that
p53 represses osterix transcription by the minimal promoter in a
DNA-binding–independent manner. In addition,
p53 − / − osteoblasts have an enhanced ability to favor osteoclast differentiation, in association
with an increase in expression of macrophage-colony stimulating factor, which is under the
control of osterix. Furthermore, inactivating p53 is sufficient to rescue the osteoblast
differentiation defects observed in mice lacking c-Abl, a p53-interacting protein. Thus,
these results identify p53 as a novel regulator of osteoblast differentiation,
osteoblast-dependent osteoclastogenesis, and bone remodeling.
229 citations
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TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
23,959 citations
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TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
18,175 citations
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TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.
Abstract: We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of ChIP-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. MACS also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available.
13,008 citations
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Ewan Birney, John A. Stamatoyannopoulos1, Anindya Dutta2, Roderic Guigó3 +317 more•Institutions (44)
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
5,091 citations
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TL;DR: This work generated induced pluripotent stem cells capable of germline transmission from murine somatic cells by transd, and demonstrated the ability of these cells to reprogram into patient-specific and disease-specific stem cells.
Abstract: If it were possible to reprogram differentiated human somatic cells into a pluripotent state, patient-specific and disease-specific stem cells could be developed. Previous work generated induced pluripotent stem (iPS) cells capable of germline transmission from murine somatic cells by transd
4,034 citations