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Stem cells

Biochemistry, Biophysics, and Structural Biology

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Full-Text Articles in Cell Biology

Tale Factors Use Two Distinct Functional Modes To Control An Essential Zebrafish Gene Expression Program, Franck Ladam, William Stanney, Ian J. Donaldson, Ozge Yildiz, Nicoletta Bobola, Charles G. Sagerstrom Jun 2018

Tale Factors Use Two Distinct Functional Modes To Control An Essential Zebrafish Gene Expression Program, Franck Ladam, William Stanney, Ian J. Donaldson, Ozge Yildiz, Nicoletta Bobola, Charles G. Sagerstrom

Open Access Articles

TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN ...


Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio May 2018

Imp3 Stabilization Of Wnt5b Mrna Facilitates Taz Activation In Breast Cancer, Sanjoy Samanta, Santosh Guru, Ameer L. Elaimy, John J. Amante, Jianhong Ou, Jun Yu, Lihua Julie Zhu, Arthur M. Mercurio

Open Access Articles

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with many aggressive cancers and implicated in the function of breast cancer stem cells (CSCs). The mechanisms involved, however, are poorly understood. We observed that IMP3 facilitates the activation of TAZ, a transcriptional co-activator of Hippo signaling that is necessary for the function of breast CSCs. The mechanism by which IMP3 activates TAZ involves both mRNA stability and transcriptional regulation. IMP3 stabilizes the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitates ...


High-Resolution Proteomic And Lipidomic Analysis Of Exosomes And Microvesicles From Different Cell Sources, Reka A. Haraszti, Marie-Cecile Didiot, Ellen Sapp, John D. Leszyk, Scott A. Shaffer, Hannah E. Rockwell, Fei Gao, Niven R. Narain, Marian Difiglia, Michael A. Kiebish, Neil Aronin, Anastasia Khvorova Nov 2016

High-Resolution Proteomic And Lipidomic Analysis Of Exosomes And Microvesicles From Different Cell Sources, Reka A. Haraszti, Marie-Cecile Didiot, Ellen Sapp, John D. Leszyk, Scott A. Shaffer, Hannah E. Rockwell, Fei Gao, Niven R. Narain, Marian Difiglia, Michael A. Kiebish, Neil Aronin, Anastasia Khvorova

Open Access Articles

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are explored for use in diagnostics, therapeutics and drug delivery. However, little is known about the relationship of protein and lipid composition of EVs and their source cells. Here, we report high-resolution lipidomic and proteomic analyses of exosomes and MVs derived by differential ultracentrifugation from 3 different cell types: U87 glioblastoma cells, Huh7 hepatocellular carcinoma cells and human bone marrow-derived mesenchymal stem cells (MSCs). We identified 3,532 proteins and 1,961 lipid species in the screen. Exosomes differed from MVs in several different areas: (a) The protein patterns of exosomes were ...


Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio Nov 2016

Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio

Open Access Articles

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that ...


Regulation Of X-Linked Gene Expression During Early Mouse Development By Rlim, Feng Wang, Jongdae Shin, Jeremy Shea, Jun Yu, Ana Boskovic, Meg Byron, Xiaochun Zhu, Alex K. Shalek, Aviv Regev, Jeanne B. Lawrence, Eduardo M. Torres, Lihua J. Zhu, Oliver J. Rando, Ingolf Bach Sep 2016

Regulation Of X-Linked Gene Expression During Early Mouse Development By Rlim, Feng Wang, Jongdae Shin, Jeremy Shea, Jun Yu, Ana Boskovic, Meg Byron, Xiaochun Zhu, Alex K. Shalek, Aviv Regev, Jeanne B. Lawrence, Eduardo M. Torres, Lihua J. Zhu, Oliver J. Rando, Ingolf Bach

Open Access Articles

Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our ...