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Stem cells

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Articles 1 - 30 of 33

Full-Text Articles in Cell Biology

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer May 2019

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer

UT GSBS Dissertations and Theses (Open Access)

Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I ...


Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley Nov 2018

Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley

Bioelectrics Publications

Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell's compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical ...


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 ...


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

University of Massachusetts Medical School Faculty Publications

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 ...


Profiling Of Pluripotency Factors In Individual Stem Cells And Early Embryos, Sarah J. Hainer, Ana Boskovic, Oliver J. Rando, Thomas G. Fazzio Mar 2018

Profiling Of Pluripotency Factors In Individual Stem Cells And Early Embryos, Sarah J. Hainer, Ana Boskovic, Oliver J. Rando, Thomas G. Fazzio

University of Massachusetts Medical School Faculty Publications

Major cell fate decisions are governed by sequence-specific transcription factors (TFs) that act in small cell populations within developing embryos. To understand how TFs regulate cell fate it is important to identify their genomic binding sites in these populations. However, current methods cannot profile TFs genome-wide at or near the single cell level. Here we adapt the CUT&RUN method to profile chromatin proteins in low cell numbers, mapping TF-DNA interactions in single cells and individual pre-implantation embryos for the first time. Using this method, we demonstrate that the pluripotency TF NANOG is significantly more dependent on the SWI/SNF ...


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 ...


Fibroblast Growth Factor Receptor Function In Muscle Stem Cells, Tashi Hackett Jan 2018

Fibroblast Growth Factor Receptor Function In Muscle Stem Cells, Tashi Hackett

Undergraduate Honors Theses

Skeletal muscle has a remarkable ability to regenerate itself following injury and this is reliant upon a group of stem cells known as muscle stem cells Muscle stem cell dysfunction contributes to variety of muscle wasting diseases and insights into mechanisms that regulate MuSC function could lead to new therapies and further our understanding of stem cell biology in general. Fibroblast Growth Factor 2 (FGF2) is a protein that regulates muscle stem cell behavior through stimulation of cell surface tyrosine receptor kinases known as Fibroblast Growth Factor Receptors (Jones, 2001). Activation of the receptors by FGF will induce intracellular signaling ...


Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald Jan 2018

Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald

Graduate College Dissertations and Theses

In the United States, metastatic breast cancer kills approximately 40,000 women and 400 men annually, and approximately 200,000 new cases of breast cancer are diagnosed each year. Worldwide, breast cancer is the leading cause of cancer deaths among women. Despite advances in the detection and treatment of metastatic breast cancer, mortality rates from this disease remain high because the fact is that once metastatic, it is virtually incurable. It is widely accepted that a major reason breast cancer continues to exhibit recurrence after remission is that current therapies are insufficient for targeting and eliminating therapy-resistant cancer cells. Emerging ...


The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers Aug 2017

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and ...


Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson Feb 2017

Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9OB −/−). Both Fgf9 knockout (Fgf9OB −/−) and the Fgf9 floxed littermates (Fgf9fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three month old ...


Histone Variant Macroh2a In The Gut And Beyond: A Study Of Intestinal Fortitude, Ryan James Cedeno Jan 2017

Histone Variant Macroh2a In The Gut And Beyond: A Study Of Intestinal Fortitude, Ryan James Cedeno

Publicly Accessible Penn Dissertations

Epigenetic factors guide chromatin remodeling during cell state transitions and confer resistance to genotoxic stressors that could induce deleterious transformations. A particularly peculiar component of the epigenome with emerging roles in fine-tuning cell identity and upholding genomic stability is the structural histone variant macroH2A. Relatively little is currently known about macroH2A’s influence on overall cell developmental potency and less still is known about macroH2A’s contributions to adult stem cell identity and function in vivo. In this work, we use induced pluripotent stem cell (iPSC) reprogramming and the murine intestinal stem cell (ISC) system to model macroH2A’s overall ...


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 ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis Aug 2016

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab Publications

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Microengineering Approaches For Regenerative Medicine, Yubing Sun May 2016

Microengineering Approaches For Regenerative Medicine, Yubing Sun

UMass Center for Clinical and Translational Science Research Retreat

Stem cells, especially human pluripotent stem cells (hPSCs), hold significant promise for modeling developmental and disease processes, drug and toxicology screening, and cell-based regenerative medicine. Most hPSC studies have so far focused on identifying extrinsic soluble factors, intracellular signaling pathways, and transcriptional regulatory networks involved in regulating hPSC behaviors. We focus on the development and applications of some novel synthetic micromechanical systems to understand the mechano-sensitive and -responsive properties of hPSCs and their functional regulation of self-renewal, directed differentiation, and survival of hPSCs. First, we have demonstrated that rigid PDMS micropost arrays (PMAs) support the maintenance of pluripotency of hPSCs ...


Expansion, Characterization, Differentiation, And Visualization Of Mc 3t3-E1 Preosteoblast Cells: An In Vitro Model To Study Bone Healing And Stem Cell-Mediated Regeneration, Jakob T. Samsel, Madhu Dhar, Austin Bow, Tom Masi May 2016

Expansion, Characterization, Differentiation, And Visualization Of Mc 3t3-E1 Preosteoblast Cells: An In Vitro Model To Study Bone Healing And Stem Cell-Mediated Regeneration, Jakob T. Samsel, Madhu Dhar, Austin Bow, Tom Masi

Chancellor’s Honors Program Projects

No abstract provided.


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 ...


Pdgf-Ab And 5-Azacytidine Induce Conversion Of Somatic Cells Into Tissue-Regenerative Multipotent Stem Cells, Vashe Chandrakanthan, Avani Yeola, Jair C. Kwan, Rema A. Oliver, Qiao Qiao, Young Chan Kang, Peter Zarzour, Dominik Beck, Lies Boelen, Ashwin Unnikrishnan, Jeanette E. Villanueva, Andrea C. Nunez, Kathy Knezevic, Cintia Palu, Rabab Nasrallah, Michael Carnell, Alex Macmillan, Renee Whan, Yan Yu, Philip Hardy, Shane T. Grey, Amadeus Gladbach, Fabien Delerue, Lars Ittner, Ralph Mobbs, Carl R. Walkley, Louise E. Purton, Robyn L. Ward, Jason W. H. Wong, Luke B. Hesson, William Walsh, John E. Pimanda Jan 2016

Pdgf-Ab And 5-Azacytidine Induce Conversion Of Somatic Cells Into Tissue-Regenerative Multipotent Stem Cells, Vashe Chandrakanthan, Avani Yeola, Jair C. Kwan, Rema A. Oliver, Qiao Qiao, Young Chan Kang, Peter Zarzour, Dominik Beck, Lies Boelen, Ashwin Unnikrishnan, Jeanette E. Villanueva, Andrea C. Nunez, Kathy Knezevic, Cintia Palu, Rabab Nasrallah, Michael Carnell, Alex Macmillan, Renee Whan, Yan Yu, Philip Hardy, Shane T. Grey, Amadeus Gladbach, Fabien Delerue, Lars Ittner, Ralph Mobbs, Carl R. Walkley, Louise E. Purton, Robyn L. Ward, Jason W. H. Wong, Luke B. Hesson, William Walsh, John E. Pimanda

Faculty of Health Sciences Publications

Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to ...


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 ...


Investigating The Fibroblastic Origin Of Skin-Derived Precursors And The Role Of Ccn2 As A Mediator Of Myofibroblastic Differentiation, Matthew Tsang May 2015

Investigating The Fibroblastic Origin Of Skin-Derived Precursors And The Role Of Ccn2 As A Mediator Of Myofibroblastic Differentiation, Matthew Tsang

Electronic Thesis and Dissertation Repository

Skin-derived precursors (SKPs) are defined as multipotent spheroid-forming cells cultured from the dermis that express markers of neural crest origin. Recent evidence suggests that tissue fibrosis can occur through the differentiation of progenitor cells into smooth muscle-like myofibroblasts. CCN2, a marker and mediator of fibrosis, is highly expressed during myofibroblast differentiation and is required for skin fibrogenesis. Here, I clarify the cellular origin of SKPs, and the molecular contribution of CCN2 in the myofibroblastic differentiation of SKPs. Using lineage tracing, I show that SKPs originate primarily from Col1a2-expressing dermal fibroblasts. Furthermore, I show that differentiation of SKPs into myofibroblasts requires ...


Molecular And Cellular Basis Of Hematopoietic Stem Cells Maintenance And Differentiation, Khanh Linh Duong Dec 2014

Molecular And Cellular Basis Of Hematopoietic Stem Cells Maintenance And Differentiation, Khanh Linh Duong

Theses and Dissertations

The blood system consists of two main lineages: myeloid and lymphoid. The myeloid system consists of cells that are part of the innate immune response while the lymphoid system consist of cells that are part of humoral response. These responses protect our bodies from foreign pathogens. Thus, malignancies in these systems often cause complications and mortality. Scientists world wide have been researching alternatives to treat hematologic disorders and have explored induced pluripotent stem cells (iPSCs) and the conversion of one cell type to another.

First, iPS cells were generated by overexpression of four transcription factors: Oct4, Sox2, Klf4 an cMyc ...


Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip Jul 2014

Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells (ISCs) in the adult Drosophila midgut can respond to tissue damage and support repair. We used genetic manipulation to increase the number of ISC-like cells in the adult midgut and performed gene expression profiling to identify potential ISC regulators. A detailed analysis of one of these potential regulators, the zinc-finger protein Charlatan, was carried out. MARCM clonal analysis and RNAi in precursor cells showed that loss of Chn function caused severe ISC division defects, including loss of EdU incorporation, phosphorylated histone 3 staining and expression of the mitotic protein Cdc2. Loss of Charlatan also led to a ...


The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller May 2014

The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller

Student Publications & Research

CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in ...


Germline Transgenic Methods For Tracking Cells And Testing Gene Function During Regeneration In The Axolotl, Shahryar Khattak, Maritta Schuez, Tobias Richter, Dunja Knapp, Saori L. Haigo, Tatiana Sandoval-Guzmán, Kristyna Hradlikova, Annett Duemmler, Ryan R. Kerney, Elly M. Tanaka Jun 2013

Germline Transgenic Methods For Tracking Cells And Testing Gene Function During Regeneration In The Axolotl, Shahryar Khattak, Maritta Schuez, Tobias Richter, Dunja Knapp, Saori L. Haigo, Tatiana Sandoval-Guzmán, Kristyna Hradlikova, Annett Duemmler, Ryan R. Kerney, Elly M. Tanaka

Biology Faculty Publications

The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum(axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we ...


Cellular Mechanisms Of Mammalian Liver Regeneration, Kilangsungla Yanger Jan 2013

Cellular Mechanisms Of Mammalian Liver Regeneration, Kilangsungla Yanger

Publicly Accessible Penn Dissertations

ABSTRACT

CELLULAR MECHANISMS OF MAMMALIAN LIVER REGENERATION

Kilangsungla Yanger

Ben Z. Stanger

The liver is an essential organ that aids in metabolic processes, protein synthesis and detoxification of harmful substances. As the centre for detoxification, the liver is able to compensate for this routine damage with its robust regenerative ability. All vertebrate livers, for example, can make up for tissue mass loss (via surgical excision of a portion of the liver) by replication of their differentiated cells within the remnant lobes. These differentiated cells include parenchymal cells such as the hepatocytes and biliary epithelial cells (BECs) and also non-parenchymal cells ...