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Articles 1 - 11 of 11

Full-Text Articles in Cell Biology

Yap Drives Cutaneous Squamous Cell Carcinoma Formation And Progression, Zoe Vincent-Mistiaen, Ahmed Elbediwy, Hannah Vanyai, Jennifer L. Cotton, Gordon Stamp, Emma Nye, Bradley Spencer-Dene, Gareth J. Thomas, Junhao Mao, Barry Thompson Sep 2018

Yap Drives Cutaneous Squamous Cell Carcinoma Formation And Progression, Zoe Vincent-Mistiaen, Ahmed Elbediwy, Hannah Vanyai, Jennifer L. Cotton, Gordon Stamp, Emma Nye, Bradley Spencer-Dene, Gareth J. Thomas, Junhao Mao, Barry Thompson

Open Access Articles

Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where ...


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 ...


Preleukemia And Leukemia-Initiating Cell Activity In Inv(16) Acute Myeloid Leukemia, John A. Pulikkan, Lucio H. Castilla Apr 2018

Preleukemia And Leukemia-Initiating Cell Activity In Inv(16) Acute Myeloid Leukemia, John A. Pulikkan, Lucio H. Castilla

Open Access Articles

Acute myeloid leukemia (AML) is a collection of hematologic malignancies with specific driver mutations that direct the pathology of the disease. The understanding of the origin and function of these mutations at early stages of transformation is critical to understand the etiology of the disease and for the design of effective therapies. The chromosome inversion inv(16) is thought to arise as a founding mutation in a hematopoietic stem cell (HSC) to produce preleukemic HSCs (preL-HSCs) with myeloid bias and differentiation block, and predisposed to AML. Studies in mice and human AML cells have established that inv(16) AML follows ...


Transient Transcriptional Silencing Alters The Cell Cycle To Promote Germline Stem Cell Differentiation In Drosophila, Pooja Flora, Sean Schowalter, Siuwah Wong-Deyrup, Matthew Degennaro, Mohamad Ali Nasrallah, Prashanth Rangan Feb 2018

Transient Transcriptional Silencing Alters The Cell Cycle To Promote Germline Stem Cell Differentiation In Drosophila, Pooja Flora, Sean Schowalter, Siuwah Wong-Deyrup, Matthew Degennaro, Mohamad Ali Nasrallah, Prashanth Rangan

Open Access Articles

Transcriptional silencing is a conserved process used by embryonic germ cells to repress somatic fate and maintain totipotency and immortality. In Drosophila, this transcriptional silencing is mediated by polar granule component (pgc). Here, we show that in the adult ovary, pgc is required for timely germline stem cell (GSC) differentiation. Pgc is expressed transiently in the immediate GSC daughter (pre-cystoblast), where it mediates a pulse of transcriptional silencing. This transcriptional silencing mediated by pgc indirectly promotes the accumulation of Cyclin B (CycB) and cell cycle progression into late-G2 phase, when the differentiation factor bag of marbles (bam) is expressed. Pgc ...


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 ...


A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page Oct 2016

A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page

Open Access Articles

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells ...


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 ...


Apontic Regulates Somatic Stem Cell Numbers In Drosophila Testes, Amanda J. Monahan, Michelle Starz-Gaiano Mar 2016

Apontic Regulates Somatic Stem Cell Numbers In Drosophila Testes, Amanda J. Monahan, Michelle Starz-Gaiano

Open Access Articles

BACKGROUND: Microenvironments called niches maintain resident stem cell populations by balancing self-renewal with differentiation, but the genetic regulation of this process is unclear. The niche of the Drosophila testis is well-characterized and genetically tractable, making it ideal for investigating the molecular regulation of stem cell biology. The JAK/STAT pathway, activated by signals from a niche component called the hub, maintains both germline and somatic stem cells.

RESULTS: This study investigated the molecular regulation of the JAK/STAT pathway in the stem cells of the Drosophila testis. We determined that the transcriptional regulator Apontic (Apt) acts in the somatic (cyst ...


Bunched And Madm Function Downstream Of Tuberous Sclerosis Complex To Regulate The Growth Of Intestinal Stem Cells In Drosophila, Yingchao Nie, Qi Li, Alla Amcheslavsky, Juan Carlos Duhart, Alexey Veraksa, Hugo Stocker, Laurel A. Raftery, Y. Tony Ip Dec 2015

Bunched And Madm Function Downstream Of Tuberous Sclerosis Complex To Regulate The Growth Of Intestinal Stem Cells In Drosophila, Yingchao Nie, Qi Li, Alla Amcheslavsky, Juan Carlos Duhart, Alexey Veraksa, Hugo Stocker, Laurel A. Raftery, Y. Tony Ip

Open Access Articles

The Drosophila adult midgut contains intestinal stem cells that support homeostasis and repair. We show here that the leucine zipper protein Bunched and the adaptor protein Madm are novel regulators of intestinal stem cells. MARCM mutant clonal analysis and cell type specific RNAi revealed that Bunched and Madm were required within intestinal stem cells for proliferation. Transgenic expression of a tagged Bunched showed a cytoplasmic localization in midgut precursors, and the addition of a nuclear localization signal to Bunched reduced its function to cooperate with Madm to increase intestinal stem cell proliferation. Furthermore, the elevated cell growth and 4EBP phosphorylation ...