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Differentiation

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Articles 1 - 26 of 26

Full-Text Articles in Cell Biology

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali Aug 2019

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali

UT GSBS Dissertations and Theses (Open Access)

Recently, a novel class of muscular dystrophy has been discovered in a family due to autosomal recessive missense mutation in POGLUT1. Mutation of this enzyme leads to decreased O-glucosyltransferase activity and impaired Notch signaling, the pathways important for skeletal muscle stem cell (satellite cells) quiescence and activation. We hypothesize that reduced POGLUT1 activity and impaired Notch signaling is causative of this limb girdle muscular dystrophy through dysfunction of muscle stem cells and myogenic progenitors.

To test this, we have used iPSCs for disease modeling and rescue experiments. Using a CRISPR based gene targeting method, we aimed to correct the point ...


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 ...


A Pitx2-Irx1 Regulatory Network Controls Dental Epithelial Stem Cell Differentiation During Tooth Development, Wenjie Yu Dec 2017

A Pitx2-Irx1 Regulatory Network Controls Dental Epithelial Stem Cell Differentiation During Tooth Development, Wenjie Yu

Theses and Dissertations

Tooth development is precisely controlled by epithelium-mesenchyme interactions, coordinated signaling pathways and associated transcription factors. Although the processes involved in tooth development are well established, details of the cellular and molecular mechanisms that control tooth development are not fully understood. One of the primary unknown mechanisms is the regulation of dental epithelial stem cells (DESCs), including DESC specification, proliferation and differentiation. In this dissertation, I have addressed this gap in knowledge by studying the role of Pituitary homeobox 2 (Pitx2) and Iroquois 1 (Irx1) in teeth at the cellular and molecular level in mice. PITX2 contains mutations of which are ...


The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv Dec 2017

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity ...


Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert Aug 2017

Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert

Electronic Thesis and Dissertation Repository

Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) with retinoic acid (RA) treatment, resulting in up-regulation of Gata6, which when translated directly activates Wnt6. Canonical Wnt signalling is required for PrE differentiation, and this, like most developmental processes, requires input from one or more additional pathways, including hedgehog (Hh). The Hh pathway is regulated by GATA6, and crosstalks positively/negatively with Wnt signalling. Ihh up-regulation in F9 cells accompanies PrE induction, but a role for GATA6 or Hh pathway activation in obligatory Wnt/ß-catenin signalling is not known. To address this, I show that RA induces Ihh and altered ...


An Embryonic Stem Cell-Specific Nurd Complex Functions Through Interaction With Wdr5, Ly-Sha Ee, Kurtis N. Mccannell, Yang Tang, Nancy Fernandes, W. Rod Hardy, Michael R. Green, Feixia Chu, Thomas G. Fazzio Jun 2017

An Embryonic Stem Cell-Specific Nurd Complex Functions Through Interaction With Wdr5, Ly-Sha Ee, Kurtis N. Mccannell, Yang Tang, Nancy Fernandes, W. Rod Hardy, Michael R. Green, Feixia Chu, Thomas G. Fazzio

Open Access Articles

The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5. Domain analyses of WDR5 reveal that the H3 binding pocket is required for interaction with MBD3C. We find ...


Global Increase In Replication Fork Speed During A P57kip2-Regulated Erythroid Cell Fate Switch, Yung Hwang, Melinda Futran, Daniel Hidalgo, Ramona Pop, Divya Ramalingam Iyer, Ralph Scully, Nicholas R. Rhind, Merav Socolovsky May 2017

Global Increase In Replication Fork Speed During A P57kip2-Regulated Erythroid Cell Fate Switch, Yung Hwang, Melinda Futran, Daniel Hidalgo, Ramona Pop, Divya Ramalingam Iyer, Ralph Scully, Nicholas R. Rhind, Merav Socolovsky

Open Access Articles

Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase-dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a ...


Kat-Independent Gene Regulation By Tip60 Promotes Esc Self-Renewal But Not Pluripotency, Diwash Acharya, Sarah J. Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A. Rivera-Perez, Thomas G. Fazzio Apr 2017

Kat-Independent Gene Regulation By Tip60 Promotes Esc Self-Renewal But Not Pluripotency, Diwash Acharya, Sarah J. Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A. Rivera-Perez, Thomas G. Fazzio

Pediatric Publications and Presentations

Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function ...


Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith Jan 2017

Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived ...


Identification Of Oxygen Optima For Mouse Trophoblast Stem Cells And Human Embryos And The Stress Responses Upon Departing Optima, Yu Yang Jan 2017

Identification Of Oxygen Optima For Mouse Trophoblast Stem Cells And Human Embryos And The Stress Responses Upon Departing Optima, Yu Yang

Wayne State University Dissertations

Low level of oxygen (O2) occurs physiologically during in vivo embryo development. As developing embryos moving from fallopian tube to uterus, oxygen level gradually decreases to ≤ 5% at the time of blastocyst implantation. Blastocysts are made of two major cell populations, trophoblast cells and inner cell mass, from which trophoblast stem cells (TSCs) and embryonic stem cells (ESCs) are derived respectively. TSCs serve as placental stem cells that later on proliferate and differentiate into placenta. Previous study has shown that 2% O2 is the optimal O2 level for mTSC in vitro growth and potency maintenance, which agrees with their low ...


Consensus Paper: Cerebellar Development, Ketty Leto, Baojin Ding, Daniel Lee Kilpatrick Dec 2016

Consensus Paper: Cerebellar Development, Ketty Leto, Baojin Ding, Daniel Lee Kilpatrick

Open Access Articles

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.


The Role Of Nadph Oxidase In Ros Mediated Differentiation, Benjamin J. Dickson Jun 2016

The Role Of Nadph Oxidase In Ros Mediated Differentiation, Benjamin J. Dickson

Electronic Thesis and Dissertation Repository

Mouse teratocarcinoma F9 cells differentiate into primitive endoderm (PrE) when treated with retinoic acid (RA) or H2O2 and these changes are accompanied by an upregulation of Wnt6 and activation of the canonical WNT/β-catenin pathway. Data from our lab shows PrE differentiation is accompanied by an increase in reactive oxygen species (ROS), which induces a conformational change in Nucleoredoxin preventing its ability to bind and inhibit Dishevelled. This in turn positively impacts on the WNT/β- catenin signaling pathway leading to differentiation. The source of endogenous ROS seen following RA treatment was investigated and members of the NADPH oxidase (NOX ...


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.


Characterization Of Embryonic Stem Cell-Differentiated Cells As Mesenchymal Stem Cells, Rachael N. Kuehn Dec 2015

Characterization Of Embryonic Stem Cell-Differentiated Cells As Mesenchymal Stem Cells, Rachael N. Kuehn

Honors Theses

Embryonic stem cells (ESCs), due to their ability to differentiate into different cell types while still maintaining a high proliferation capacity, have been considered as a potential cell source in regenerative medicine. However, current ESC differentiation methods are low yielding and create heterogeneous cell populations. If transplanted in the human body, differentiated ESCs could be rejected by the immune system, form tumors, or may not function normally within the human body. On the other hand, mesenchymal stem cells (MSCs), a type of adult stem cell typically derived from bone marrow, have proved to be excellent candidates in clinical applications due ...


Activation Of Nf-Κb Transcription Factor During In Vitro Differentiation Of Mouse Embryonic Stem Cells, Natalya A. Ortolano May 2015

Activation Of Nf-Κb Transcription Factor During In Vitro Differentiation Of Mouse Embryonic Stem Cells, Natalya A. Ortolano

Honors Theses

Embryonic stem cells (ESCs) are a promising cell source for regenerative medicine. However, recent studies indicated that ESCs and ESC-derived cells (ESC-DCs) lack functional innate immunity against various pathogens and inflammatory cytokines. This presents a barrier to clinical application, as ESC-DCs would be placed in a wound site and exposed to pathogens and inflammatory cytokines. Using mouse ESCs (mESCs) as a model, we recently demonstrated that they are deficient in expressing type I interferons (IFN) and inflammatory cytokines. To determine the molecular basis for this finding, this study examined the activation state of nuclear factor-κB (NF-κB), a transcription factor that ...


Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin Apr 2015

Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin

Electronic Thesis and Dissertation Repository

ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with ...


The Nuclear Factor Of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is A Repressor Of Chondrogenesis, Ann M. Ranger, Louis C. Gerstenfeld, Jinxi Wang, Tamiyo Kon, Hyunsu Bae, Ellen M. Gravallese, Melvin J. Glimcher, Laurie H. Glimcher Apr 2015

The Nuclear Factor Of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is A Repressor Of Chondrogenesis, Ann M. Ranger, Louis C. Gerstenfeld, Jinxi Wang, Tamiyo Kon, Hyunsu Bae, Ellen M. Gravallese, Melvin J. Glimcher, Laurie H. Glimcher

Ellen M. Gravallese

Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate ...


Altered Connexin 43 Expression Underlies Age-Dependent Decrease Of Regulatory T Cell Suppressor Function In Nonobese Diabetic Mice, Michel Kuczma, Cong-Yi Wang, Leszek Ignatowicz, Robert Gourdi, Piotr Kraj Jan 2015

Altered Connexin 43 Expression Underlies Age-Dependent Decrease Of Regulatory T Cell Suppressor Function In Nonobese Diabetic Mice, Michel Kuczma, Cong-Yi Wang, Leszek Ignatowicz, Robert Gourdi, Piotr Kraj

Biological Sciences Faculty Publications

Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell–mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (Tregs) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Tregs in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory ...


P120-Catenin Regulates Rest And Corest, And Modulates Mouse Embryonic Stem Cell Differentiation, Moonsup Lee Dec 2014

P120-Catenin Regulates Rest And Corest, And Modulates Mouse Embryonic Stem Cell Differentiation, Moonsup Lee

UT GSBS Dissertations and Theses (Open Access)

The canonical-Wnt pathway and beta-catenin have been extensively studied to determine their contributions to stem cell biology, but less is known about p120-catenin in the nuclear compartment. P120 is developmentally required as a consequence of its biochemical and functional interactions with cadherins, small-GTPases and transcriptional regulators. We report here that p120-catenin binds to and negatively regulates REST and CoREST, that others have indicated form a repressive complex having diverse key roles in developmental and pathologic gene regulation. We thus provide the first evidence for a direct upstream modulator of REST/CoREST function. Using mouse embryonic stem cells (mESCs), mammalian cell ...


Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang Aug 2014

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important ...


The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef Jan 2014

The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef

Electronic Thesis and Dissertation Repository

The human placenta of different gestational ages is a readily available source for isolation of adult mesenchymal stem cell (MSC) for potential use in regenerative therapies. The chorionic villous region, the largest component of a placenta that interfaces with the maternal circulation, is a rich source of placental MSCs (PMSCs). To remain multipotent, PMSCs are best maintained in culture conditions that mimic the in vivo microenvironment. Insulin like growth factors (IGFs, IGF-I and -II) and oxygen tension are two of the most important microenvironmental factors in the placenta. They are of low concentration or tension respectively, at early gestation, and ...


Role Of Stat3 In Keratinocyte Stem Cells During Skin Tumorigenesis, Dharanija Rao Aug 2012

Role Of Stat3 In Keratinocyte Stem Cells During Skin Tumorigenesis, Dharanija Rao

UT GSBS Dissertations and Theses (Open Access)

STATs play crucial roles in a wide variety of biological functions, including development, proliferation, differentiation, migration and in cancer development. In the present study, we examined the impact of Stat3 deletion or activation on behavior of keratinocytes, including keratinocyte stem cells (KSCs). Deletion of Stat3 specifically in the bulge region of the hair follicle using K15.CrePR1 X Stat3fl/fl mice led to decreased tumor development by altering survival of bulge region KSCs. To further understand the role of KSCs in skin tumorigenesis, K5.Stat3C transgenic (Tg) mice which express a constitutively active/dimerized form of Stat3 called Stat3C ...


A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel Jan 2012

A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel

CMC Senior Theses

The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells ...


Hdac3 Is A Critical Regulator Of Neural Crest Progenitor Cell Biology, Nikhil Singh Jan 2012

Hdac3 Is A Critical Regulator Of Neural Crest Progenitor Cell Biology, Nikhil Singh

Publicly Accessible Penn Dissertations

Vertebrate embryogenesis relies on the coordinated development of multiple progenitor cell pools. Specific transcriptional programs regulate the specification, expansion, migration and eventual differentiation of these progenitor cell populations, and tight control of these programs is essential for normal development to occur. Class I histone deacetylases (Hdacs), including Hdac3, play critical roles in regulating gene transcription, through both epigenetic and non-epigenetic means. In this dissertation, I use mouse genetics to explore the previously undescribed role of Hdac3 in regulating neural crest progenitor cell behavior. By genetically deleting Hdac3 in premigratory neural crest cells, I use in vivo and ex vivo techniques ...


Development Of A High Throughput Assay To Optimize Hematopoietic Differentiation Of Human Pluripotent Stem Cells, Joel Thomas Outten Jan 2012

Development Of A High Throughput Assay To Optimize Hematopoietic Differentiation Of Human Pluripotent Stem Cells, Joel Thomas Outten

Publicly Accessible Penn Dissertations

Human embryonic stem cells (hESCs) offer the potential to develop in vitro protocols for the generation of any human somatic cell. In order for protocols to allow for both comprehension of underlying developmental mechanics and future clinical application, they will need to rely upon efficient differentiation of cells without the reliance upon animal-derived components. This thesis presents the development of a 96-well plate culture system that allows 4-color, flow cytometry based high throughput screening of defined, serum-free hESC differentiation conditions. In the first portion, broad applicability is proven by demonstrating highly efficient differentiation toward the three primary germ layers. Using ...


The Nuclear Factor Of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is A Repressor Of Chondrogenesis, Ann M. Ranger, Louis C. Gerstenfeld, Jinxi Wang, Tamiyo Kon, Hyunsu Bae, Ellen M. Gravallese, Melvin J. Glimcher, Laurie H. Glimcher Jan 2000

The Nuclear Factor Of Activated T Cells (Nfat) Transcription Factor Nfatp (Nfatc2) Is A Repressor Of Chondrogenesis, Ann M. Ranger, Louis C. Gerstenfeld, Jinxi Wang, Tamiyo Kon, Hyunsu Bae, Ellen M. Gravallese, Melvin J. Glimcher, Laurie H. Glimcher

Rheumatology Publications and Presentations

Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate ...