Journal ArticlebioRxiv · October 9, 2024
The upper airway, particularly the nasal and oral mucosal epithelium, serves as a primary barrier for microbial interactions throughout life. Specialized niches like the anterior nares and the tooth are especially susceptible to dysbiosis and chronic infla ...
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Journal ArticlebioRxiv · September 8, 2024
Protein S-palmitoylation is a reversible lipophilic posttranslational modification regulating a diverse number of signaling pathways. Within transmembrane proteins (TMPs), S-palmitoylation is implicated in conditions from inflammatory disorders to respirat ...
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Journal ArticleJ Proteome Res · August 2, 2024
Proteins undergo reversible S-acylation via a thioester linkage in vivo. S-palmitoylation, modification by C16:0 fatty acid, is a common S-acylation that mediates critical protein-membrane and protein-protein interactions. The most widely used S-acylation ...
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Journal ArticlebioRxiv · June 26, 2024
Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. ...
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Journal ArticleCell Rep · April 23, 2024
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation ...
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Journal ArticleDev Cell · April 8, 2024
Tissue repair requires a highly coordinated cellular response to injury. In the lung, alveolar type 2 cells (AT2s) act as stem cells to replenish both themselves and alveolar type 1 cells (AT1s); however, the complex orchestration of stem cell activity aft ...
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Journal ArticleFront Immunol · 2024
INTRODUCTION: Environmental exposures and experimental manipulations can alter the ontogenetic composition of tissue-resident macrophages. However, the impact of these alterations on subsequent immune responses, particularly in allergic airway diseases, re ...
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Journal ArticleAm J Respir Cell Mol Biol · December 2023
Single-cell RNA sequencing (scRNA-seq) of BAL cells has provided insights into coronavirus disease (COVID-19). However, reports have been limited by small patient cohorts. We performed a meta-analysis of BAL scRNA-seq data from healthy control subjects (n ...
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Journal ArticleJ Clin Invest · November 15, 2023
Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms derived from various sources, including adult, fetal, and induced pluripotent stem cells, hav ...
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Journal ArticleCell Stem Cell · November 2, 2023
Organ regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusi ...
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Journal ArticleNat Microbiol · October 2023
The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. ...
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Journal ArticleAm J Respir Cell Mol Biol · September 2023
Targeted delivery of transgenes to tissue-resident stem cells and related niches offers avenues for interrogating pathways and editing endogenous alleles for therapeutic interventions. Here, we survey multiple adeno-associated virus (AAV) serotypes, admini ...
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Journal ArticleAm J Physiol Lung Cell Mol Physiol · September 1, 2023
Pompe disease is an autosomal recessive glycogen storage disease caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)-an enzyme responsible for hydrolyzing lysosomal glycogen. GAA deficiency results in systemic lysosomal glycogen accum ...
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Journal ArticleDevelopment · August 1, 2023
Purushothama Rao Tata is an Assistant Professor in the Department of Cell Biology at Duke University Medical Center. His lab is focussed on understanding the cellular basis of cell plasticity and self-organization in regeneration and tumorigenesis, using t ...
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Journal ArticleProc Natl Acad Sci U S A · June 13, 2023
Using scRNA-seq and microscopy, we describe a cell that is enriched in the lower airways of the developing human lung and identified by the unique coexpression of SCGB3A2/SFTPB/CFTR. To functionally interrogate these cells, we apply a single-cell barcode-b ...
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Journal ArticleNat Med · June 2023
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of indiv ...
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Journal ArticleCell Rep · November 8, 2022
In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. ...
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Journal ArticleSci Signal · October 25, 2022
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccin ...
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Journal ArticleiScience · October 21, 2022
Epithelial cells of diverse tissues are characterized by the presence of a single apical domain. In the lung, electron microscopy studies have suggested that alveolar type-2 epithelial cells (AT2s) en face multiple alveolar sacs. However, apical and basola ...
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Journal ArticleCold Spring Harb Perspect Biol · October 3, 2022
Lung epithelium, the lining that covers the inner surface of the respiratory tract, is directly exposed to the environment and thus susceptible to airborne toxins, irritants, and pathogen-induced damages. In adult mammalian lungs, epithelial cells are gene ...
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Journal ArticleJ Dent Res · October 2022
Oral and craniofacial tissues are uniquely adapted for continuous and intricate functioning, including breathing, feeding, and communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, variously composed of ...
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Journal ArticleDevelopment · September 15, 2022
Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mou ...
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Journal ArticleSTAR Protoc · June 17, 2022
Alveolar type 2 cells (AT2s) serve as stem cells of the alveoli and restore cell numbers after injury. Here, we describe a detailed protocol for the isolation, purification, and culture of murine and human AT2s. We have developed chemically defined and str ...
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Journal ArticleCell Rep · May 10, 2022
Mesenchymal progenitors of the lateral plate mesoderm give rise to various cell fates within limbs, including a heterogeneous group of muscle-resident mesenchymal cells. Often described as fibro-adipogenic progenitors, these cells are key players in muscle ...
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Journal ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology · May 1, 2022
Pompe disease is an autosomal recessive glycogen storage disease caused by mutations in alpha-glucosidase (GAA) - an enzyme responsible of hydrolyzing lysosomal glycogen. GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disru ...
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Journal ArticleNature · April 2022
Mapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs ...
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Journal ArticleDev Cell · February 7, 2022
Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been i ...
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Journal ArticleFront Bioeng Biotechnol · 2022
The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is ...
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Journal ArticleAdv Sci (Weinh) · October 2021
Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation ...
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Journal ArticleElife · July 19, 2021
Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ...
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Journal ArticleNat Commun · July 14, 2021
Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteri ...
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Journal ArticleEMBO Rep · July 5, 2021
Epithelial tissues respond to a wide variety of environmental and genotoxic stresses. As an adaptive mechanism, cells can deviate from their natural paths to acquire new identities, both within and across lineages. Under extreme conditions, epithelial tiss ...
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Journal ArticleNature · July 2021
COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart auto ...
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Journal ArticleAm J Respir Crit Care Med · May 15, 2021
Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full characterization of CFTR expression in normal human airway ...
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Journal ArticleNat Med · March 2021
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. W ...
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Journal ArticlebioRxiv · February 25, 2021
The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellu ...
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Journal Article · 2021
ABSTRACTBackground Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here we profile proliferation kinetics of cardiac endothelial cel ...
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Journal Article · 2021
Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ...
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Journal ArticleCell Rep · December 22, 2020
Tissue regeneration requires coordinated and dynamic remodeling of stem and progenitor cells and the surrounding niche. Although the plasticity of epithelial cells has been well explored in many tissues, the dynamic changes occurring in niche cells remain ...
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Journal ArticlebioRxiv · December 16, 2020
While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low proba ...
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Journal ArticleImmunity · December 15, 2020
Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center coh ...
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Journal ArticleCell Stem Cell · December 3, 2020
Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. The absence of ex vivo models of human alveolar epithelium is hindering an understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here, we repo ...
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Journal ArticleElife · November 12, 2020
We present an oblique plane microscope (OPM) that uses a bespoke glass-tipped tertiary objective to improve the resolution, field of view, and usability over previous variants. Owing to its high numerical aperture optics, this microscope achieves lateral a ...
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Journal ArticleEMBO J · November 2, 2020
Stem cell-derived organoid models have emerged as a valuable tool for studying organogenesis, cell-to-cell stromal communication and disease. In this issue, Vazquez-Armendariz et al (2020) report a murine lung stem cell-based bronchioalveolar organoid syst ...
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Journal ArticleNat Cell Biol · August 2020
Stem cells undergo dynamic changes in response to injury to regenerate lost cells. However, the identity of transitional states and the mechanisms that drive their trajectories remain understudied. Using lung organoids, multiple in vivo repair models, sing ...
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Journal ArticleCell · July 23, 2020
The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 ( ...
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Journal ArticleCell · May 28, 2020
There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert ...
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Journal ArticleNat Med · May 2020
We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and i ...
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Journal ArticleElife · December 12, 2019
Human mutations in the dystroglycan complex (DGC) result in not only muscular dystrophy but also cognitive impairments. However, the molecular architecture critical for the synaptic organization of the DGC in neurons remains elusive. Here, we report Inhibi ...
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ConferenceCancer Research · July 1, 2019
AbstractSquamous cell carcinoma (SCC) remains among the most treatment-refractory of human cancers, reflecting in part a limited understanding of the key pathways and mechanisms that drive this disease. The ...
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Journal ArticleStem Cell Reports · April 9, 2019
Inflammatory responses are known to facilitate tissue recovery following injury. However, the precise mechanisms that enhance lung alveolar regeneration remain unclear. Here, using an organoid-based screening assay, we find that interleukin-1 (IL-1) and tu ...
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Journal ArticleProc Natl Acad Sci U S A · January 29, 2019
Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung ...
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Journal Article · 2019
Stem cell senescence is often seen as an age associated pathological state in which cells acquire an abnormal and irreversible state. Here, we show that alveolar stem cell differentiation during lung regeneration involves a unique previously uncharacterize ...
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Journal ArticleNature · August 2018
The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify ...
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Journal ArticleDev Cell · May 21, 2018
Organisms have developed cellular "antennas" to sense, interpret, and integrate environmental stimuli. In a recent issue of Science, Sui et al. (2018) demonstrate that discrete clusters of pulmonary neuroendocrine cells in the lung can sense airborne aller ...
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Journal ArticleCell Stem Cell · May 3, 2018
Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single-cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the ...
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Journal ArticleAm J Pathol · May 2018
Improved tools have led to a burgeoning understanding of lung regeneration in mice, but it is not yet known how these insights may be relevant to acute lung injury in humans. We report in detail two cases of fulminant idiopathic acute lung injury requiring ...
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Journal ArticleDev Cell · March 26, 2018
We show that the loss or gain of transcription factor programs that govern embryonic cell-fate specification is associated with a form of tumor plasticity characterized by the acquisition of alternative cell fates normally characteristic of adjacent organs ...
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Journal ArticleCell Stem Cell · December 7, 2017
Precise lineage trajectories and the cellular sources that contribute to regeneration after injury are largely unknown in many tissues. In this issue of Cell Stem Cell, Gadye et al. (2017) and Lin et al. (2017) show that olfactory epithelial cells transit ...
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Journal ArticleDev Biol · April 1, 2017
Wnt proteins are critical for embryonic cardiogenesis and cardiomyogenesis by regulating different intracellular signalling pathways. Whereas canonical Wnt/β-catenin signalling is required for mesoderm induction and proliferation of cardiac progenitor cell ...
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Journal ArticleDevelopment · March 1, 2017
In contrast to a prior emphasis on the finality of cell fate decisions in developmental systems, cellular plasticity is now emerging as a general theme in the biology of multiple adult organ systems. In the lung, lineage tracing has been used to identify d ...
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Journal ArticleCancer Cell · January 9, 2017
Loss-of-function mutations in SWI/SNF chromatin-remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here, we reveal that ACTL6A, encoding an SWI/SNF subunit linked to stem cell and progenitor ce ...
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Journal ArticleCurr Opin Cell Biol · December 2016
Cell identity is a fundamental feature of cells. Tissues are often organized into cellular hierarchies characterized by progressive differentiation and developmental commitment. However, it is been historically evident that the cells of many organisms of v ...
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Journal ArticleCell Stem Cell · December 1, 2016
Feedback signals from daughter cells to stem cells are well studied and known to provide important feedback cues. Emerging evidence shows that stem cells also send feedforward signals to their progeny. Complex circuits involving both negative and positive ...
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Journal ArticleCell Stem Cell · August 4, 2016
Functional modeling of many adult epithelia is limited by the difficulty in maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell popul ...
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Journal ArticleNature · July 30, 2015
Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation. Recentl ...
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Journal ArticleCell Stem Cell · February 5, 2015
Following injury, stem cells restore normal tissue architecture by producing the proper number and proportions of differentiated cells. Current models of airway epithelial regeneration propose that distinct cytokeratin 8-expressing progenitor cells, arisin ...
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Journal ArticleAm J Respir Cell Mol Biol · December 2013
Tissue-specific transgene expression using tetracycline (tet)-regulated promoter/operator elements has been used to revolutionize our understanding of cellular and molecular processes. However, because most tet-regulated mouse strains use promoters of gene ...
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Journal ArticleNature · November 14, 2013
Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells ...
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Journal ArticleGenes Dev · January 15, 2013
The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, we generated an expression signature associated wit ...
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Journal ArticleStem Cell Reports · 2013
Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has b ...
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Journal ArticleNucleic Acids Res · May 2011
The miR-290 cluster is expressed in embryonic stem cells (ESCs) and is important for the maintenance of pluripotency, but little is known about the mechanisms regulating the early embryonic microRNA cluster (EEmiRC) expression. Here we report the identific ...
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Journal ArticleCirc Res · June 25, 2010
Growth factor signaling is required for cellular differentiation, tissue morphogenesis, and tissue homeostasis. Misregulation of intracellular signal transduction can lead to developmental defects during embryogenesis or particular diseases in the adult. O ...
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