43,911 results match your criteria mice lacking

Selective acetyl-CoA carboxylase 1 inhibitor improves hepatic steatosis and hepatic fibrosis in a pre-clinical NASH model.

J Pharmacol Exp Ther 2021 Sep 17. Epub 2021 Sep 17.

Takeda Pharmaceutical Company Limited, United States

Acetyl-CoA carboxylase (ACC) 1 and ACC2 are essential rate-limiting enzymes that synthesize malonyl-CoA (M-CoA) from acetyl-CoA. ACC1 is predominantly expressed in lipogenic tissues and regulates the lipogenesis (DNL) flux. It is upregulated in the liver of patients with nonalcoholic fatty liver disease (NAFLD), ultimately leading to the formation of fatty liver. Read More

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September 2021

Hepatic Regulator of G Protein Signaling 6 (RGS6) drives non-alcoholic fatty liver disease by promoting oxidative stress and ATM-dependent cell death.

Redox Biol 2021 Aug 28;46:102105. Epub 2021 Aug 28.

Centre of Biomedical Research, Sanjay Gandhi Post-Graduate Institute of Medical Sciences Campus, Raebareli Road, Lucknow, Uttar Pradesh, 226014, India. Electronic address:

The pathophysiological mechanism(s) driving non-alcoholic fatty liver disease, the most prevalent chronic liver disease globally, have yet to be fully elucidated. Here, we identify regulator of G protein signaling 6 (RGS6), up-regulated in the livers of NAFLD patients, as a critical mediator of hepatic steatosis, fibrosis, inflammation, and cell death. Human patients with high hepatic RGS6 expression exhibited a corresponding high inflammatory burden, pronounced insulin resistance, and poor liver function. Read More

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Involvement of GPR37L1 in murine blood pressure regulation and human cardiac disease pathophysiology.

Am J Physiol Heart Circ Physiol 2021 Sep 17. Epub 2021 Sep 17.

Molecular Pharmacology Laboratory, Victor Chang Cardiac Research Institute, NSW, Australia.

Multiple mouse lines lacking the orphan G protein-coupled receptor, GPR37L1, have elicited disparate cardiovascular phenotypes. The first published Gpr37l1 knockout mice study (1) indicated a marked elevation in systolic blood pressure (SBP; ~60 mmHg), revealing a potential therapeutic opportunity. The phenotype differs from our independently generated knockout line, where male mice exhibited equivalent baseline blood pressure to wildtype (2, 3). Read More

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September 2021

Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes.

J Immunother Cancer 2021 Sep;9(9)

Immunology, Okayama University of Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

Background: Metformin (Met) is the first-line treatment for type 2 diabetes mellitus and plays an effective role in treating various diseases, such as cardiovascular disease, neurodegenerative disease, cancer, and aging. However, the underlying mechanism of Met-dependent antitumor immunity remains to be elucidated.

Methods: MitoTEMPO, a scavenger of mitochondrial superoxide, abolished the antitumor effect of Met, but not antiprogrammed cell death (PD-1) antibody (Ab) treatment. Read More

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September 2021

Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis.

Eur Heart J 2021 Sep 16. Epub 2021 Sep 16.

Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Strada Vicinale Via delle Corse, Perugia 06132, Italy.

Aims : Platelets participate in atherogenesis with mechanisms not yet fully clarified. Vascular wall MMP-2 is involved in the arterial remodelling accompanying atherosclerosis. Platelets contain and release MMP-2 but no informations are available on its role in atherosclerotic lesion formation. Read More

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September 2021

Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice.

J Thorac Dis 2021 Aug;13(8):4650-4660

State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Avian influenza A (H7N9) virus has caused more than 1,500 cases of human infection since its emergence in early 2013. Displaying little or no pathogenicity in poultry, but a 40% case-fatality rate in humans, five waves of H7N9 human infections occurred in China during 2013-2017, caused solely by a low pathogenicity strain. However, avian isolates possessing a polybasic connecting peptide in the hemagglutinin (HA) protein were detected in mid-2016, indicating that a highly pathogenic virus had emerged and was co-circulating with the low pathogenicity strains. Read More

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Homeostatic control of nuclear-encoded mitochondrial gene expression by the histone variant H2A.Z is essential for neuronal survival.

Cell Rep 2021 Sep;36(11):109704

Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada. Electronic address:

Histone variants are crucial regulators of chromatin structure and gene transcription, yet their functions within the brain remain largely unexplored. Here, we show that the H2A histone variant H2A.Z is essential for neuronal survival. Read More

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September 2021

Trypanosoma brucei triggers a broad immune response in the adipose tissue.

PLoS Pathog 2021 Sep 15;17(9):e1009933. Epub 2021 Sep 15.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Read More

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September 2021

The viral ORF3 protein is required for hepatitis E virus apical release and efficient growth in polarized hepatocytes and humanized mice.

J Virol 2021 Sep 15:JVI0058521. Epub 2021 Sep 15.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Hepatitis E virus (HEV), an enterically transmitted RNA virus, is a major cause of acute hepatitis worldwide. Additionally, HEV genotype (gt) 3 can frequently persist in immunocompromised individuals with an increased risk for developing severe liver disease. Currently, no HEV-specific treatment is available. Read More

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September 2021

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis.

Theranostics 2021 4;11(18):8692-8705. Epub 2021 Aug 4.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.

Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents. To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Read More

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AAV-Mediated Expression of Human VEGF, TNF-α, and IL-6 Induces Retinal Pathology in Mice.

Transl Vis Sci Technol 2021 Sep;10(11):15

Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.

Purpose: Retinopathies display complex pathologies, including vasculopathies, inflammation, and fibrosis, leading ultimately to visual impairment. However, animal models accurately reflecting these pathologies are lacking. In this study, we evaluate the suitability of using Adeno-associated virus (AAV)-mediated long-term expression of cytokines to establish retinal pathology in the murine retina. Read More

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September 2021

Intestinal antiviral signaling is controlled by autophagy gene independent of the microbiota.

Autophagy 2021 Sep 14:1-16. Epub 2021 Sep 14.

Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.

Mutations in the macroautophagy/autophagy gene are responsible for Vici syndrome, a human genetic disease characterized by combined immunodeficiency. Previously, we found that mice exhibit hyperinflammation in the lungs mediated by IL1B/IL-1β and TNF/TNFα, resulting in resistance to influenza. Here, we find that disruption of results in protection against multiple enteric viruses including norovirus and rotavirus. Read More

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September 2021

Epo/EpoR signaling in osteoprogenitor cells is essential for bone homeostasis and Epo-induced bone loss.

Bone Res 2021 Sep 13;9(1):42. Epub 2021 Sep 13.

Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.

High erythropoietin (Epo) levels are detrimental to bone health in adult organisms. Adult mice receiving high doses of Epo lose bone mass due to suppressed bone formation and increased bone resorption. In humans, high serum Epo levels are linked to fractures in elderly men. Read More

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September 2021

Expression profiling of ovarian BMP antagonists reveals the potential interaction between TWSG1 and the chordin subfamily in the ovary.

Mol Cell Endocrinol 2021 Sep 11;538:111457. Epub 2021 Sep 11.

Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan. Electronic address:

The TGF-β superfamily members and their antagonists comprise an indispensable system that controls mammalian ovarian development in a sophisticated manner. In contrast to a plethora of studies on the ovary-expressed TGF-β superfamily members, knowledge regarding their antagonists, including their expression profiles and antagonism preferences, is still lacking. Using quantitative PCR in rats and transcriptomic dataset comparisons in mice and humans, we set out to characterize the relative expression levels of most antagonists in the mammalian ovary. Read More

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September 2021

Acid-sensing ion channels modulate bladder nociception.

Am J Physiol Renal Physiol 2021 09 13. Epub 2021 Sep 13.

Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

Sensitization of neuronal pathways and persistent afferent drive are major contributors to somatic and visceral pain. However, the underlying mechanisms that govern whether afferent signaling will give rise to sensitization and pain are not fully understood. In the current report, we investigated the contribution of acid-sensing ion channels (ASICs) to bladder nociception in a model of chemical cystitis induced by cyclophosphamide (CYP). Read More

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September 2021

Tetraspanin CD53 modulates lymphocyte trafficking but not systemic autoimmunity in Lyn-deficient mice.

Immunol Cell Biol 2021 Sep 12. Epub 2021 Sep 12.

Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC, Australia.

The leukocyte-restricted tetraspanin CD53 has been shown to promote lymphocyte homing to lymph nodes and myeloid cell recruitment to acutely inflamed peripheral organs, and accelerate the onset of immune-mediated disease. However, its contribution in the setting of chronic systemic autoimmunity has not been investigated. We made use of the Lyn autoimmune model, generating Cd53 Lyn mice, and compared trafficking of immune cells into secondary lymphoid organs and systemic autoimmune disease development with mice lacking either gene alone. Read More

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September 2021

A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow.

Dis Model Mech 2021 Sep 13. Epub 2021 Sep 13.

Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.

In hypoplastic left heart syndrome (HLHS), the mechanisms leading to left heart hypoplasia and their associated fetal abnormalities are largely unknown. Current animal models have limited utility in resolving these questions as they either do not fully reproduce the cardiac phenotype, do not survive to term, and/or have very low disease penetrance. Here, we report the development of a surgically-induced mouse model of HLHS that overcomes these limitations. Read More

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September 2021

Murine cancer cachexia models replicate elevated catabolic pembrolizumab clearance in humans.

JCSM Rapid Commun 2021 Jul-Dec;4(2):232-244. Epub 2021 Feb 9.

Division of Pharmaceutics and Pharmacology, College of Pharmacy The Ohio State University Columbus OH USA.

Background: Monoclonal antibody (mAb) immune checkpoint inhibitor (ICI) therapies have dramatically impacted oncology this past decade. However, only about one-third of patients respond to treatment, and biomarkers to predict responders are lacking. Recent ICI clinical pharmacology data demonstrate high baseline drug clearance (CL) significantly associates with shorter overall survival, independent of ICI exposure, in patients receiving ICI mAb therapies. Read More

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February 2021

A Central Role for Atg5 in Microbiota-Dependent Foxp3 RORγt Treg Cell Preservation to Maintain Intestinal Immune Homeostasis.

Front Immunol 2021 26;12:705436. Epub 2021 Aug 26.

Department of Molecular Immunology, Ruhr-University Bochum, Bochum, Germany.

Autophagy is an evolutionary conserved catabolic pathway that ensures the degradation of intracellular components. The autophagic pathway is regulated by autophagy-related (Atg) proteins that govern formation of double-membraned vesicles called autophagosomes. Autophagy deficiency in regulatory T (Treg) cells leads to increased apoptosis of these cells and to the development of autoimmune disorders, predominantly characterized by intestinal inflammation. Read More

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Impaired B Cell Apoptosis Results in Autoimmunity That Is Alleviated by Ablation of Btk.

Front Immunol 2021 26;12:705307. Epub 2021 Aug 26.

Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, United States.

While apoptosis plays a role in B-cell self-tolerance, its significance in preventing autoimmunity remains unclear. Here, we report that dysregulated B cell apoptosis leads to delayed onset autoimmune phenotype in mice. Our longitudinal studies revealed that mice with B cell-specific deletion of pro-apoptotic Bim ( ) have an expanded B cell compartment with a notable increase in transitional, antibody secreting and recently described double negative (DN) B cells. Read More

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PEN Receptor GPR83 in Anxiety-Like Behaviors: Differential Regulation in Global vs Amygdalar Knockdown.

Front Neurosci 2021 26;15:675769. Epub 2021 Aug 26.

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Anxiety disorders are prevalent across the United States and result in a large personal and societal burden. Currently, numerous therapeutic and pharmaceutical treatment options exist. However, drugs to classical receptor targets have shown limited efficacy and often come with unpleasant side effects, highlighting the need to identify novel targets involved in the etiology and treatment of anxiety disorders. Read More

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Coagulation, Protease-Activated Receptors, and Diabetic Kidney Disease: Lessons from eNOS-Deficient Mice.

Tohoku J Exp Med 2021 ;255(1):1-8

Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences.

Endothelial nitric oxide synthase (eNOS) dysfunction is known to exacerbate the progression and prognosis of diabetic kidney disease (DKD). One of the mechanisms through which this is achieved is that low eNOS levels are associated with hypercoagulability, which promotes kidney injury. In the extrinsic coagulation cascade, the tissue factor (factor III) and downstream coagulation factors, such as active factor X (FXa), exacerbate inflammation through activation of the protease-activated receptors (PARs). Read More

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January 2021

Mitochondrial bioenergetics boost macrophages activation promoting liver regeneration in metabolically compromised animals.

Hepatology 2021 Sep 12. Epub 2021 Sep 12.

Transplant Coordination Unit. Marqués de Valdecilla University Hospital-IDIVAL. Cantabria University, Santander, Spain.

Background And Aims: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early post-transplantation organ failure, as mitochondrial respiration and ATP production are affected. Shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing Methylation-controlled J protein (MCJ) in three pre-clinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. Read More

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September 2021

Effect of blueberry (Vaccinium virgatum) extract on depressive-like behavior and metabolic serum alterations in lipopolysaccharide-challenged mice.

J Food Biochem 2021 Sep 12:e13920. Epub 2021 Sep 12.

Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil.

In the present study, we aimed to investigate the protective effect of blueberry extract on behavioral, biochemical, and morphological changes in an experimental model of lipopolysaccharide (LPS)-induced depressive behavior. Male Swiss mice were pretreated with the vehicle, fluoxetine (20 mg/kg), or Vaccinium virgatum extract (100 mg/kg and 200 mg/kg) for seven days. On day 7, the animals were administered an LPS injection (0. Read More

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September 2021

Accurate Dosimetry for Radiobiology.

Int J Radiat Oncol Biol Phys 2021 Sep 9. Epub 2021 Sep 9.

Medical Radiation Research Center, Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705. Electronic address:

Purpose: Accurate radiation dose is required to ensure reproducibility in establishing the radiobiological effect in biological systems among institutions. The dose should be the most precise and accurate parameter of the entire process. The goal is a system to provide uniform radiation dose verification among institutions that is traceable to NIST through an ADCL. Read More

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September 2021

Fasting blood glucose as a predictor of mortality: Lost in translation.

Cell Metab 2021 Sep 8. Epub 2021 Sep 8.

Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA. Electronic address:

Aging leads to profound changes in glucose homeostasis, weight, and adiposity, which are considered good predictors of health and survival in humans. Direct evidence that these age-associated metabolic alterations are recapitulated in animal models is lacking, impeding progress to develop and test interventions that delay the onset of metabolic dysfunction and promote healthy aging and longevity. We compared longitudinal trajectories, rates of change, and mortality risks of fasting blood glucose, body weight, and fat mass in mice, nonhuman primates, and humans throughout their lifespans and found similar trajectories of body weight and fat in the three species. Read More

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September 2021

Metabolic control of sensory neuron survival by the p75 neurotrophin receptor in Schwann cells.

J Neurosci 2021 Sep 7. Epub 2021 Sep 7.

Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, USA

We report that the neurotrophin receptor p75 contributes to sensory neuron survival through the regulation of cholesterol metabolism in Schwann cells. Selective deletion of p75 in mouse Schwann cells of either sex resulted in a 30% loss of dorsal root ganglia (DRG) neurons and diminished thermal sensitivity. P75 regulates Schwann cell cholesterol biosynthesis in response to BDNF, forming a co-receptor complex with ErbB2 and activating ErbB2-mediated stimulation of SREBP2, a master regulator of cholesterol synthesis. Read More

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September 2021

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

Osteoarthritis Cartilage 2021 Sep 16. Epub 2021 Sep 16.

Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. Electronic address:

Objective: To investigate the role of Cacalmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA).

Methods: Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2 mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i. Read More

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September 2021

Postnatal Sox6 regulates synaptic function of cortical parvalbumin-expressing neurons.

J Neurosci 2021 Sep 9. Epub 2021 Sep 9.

Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.

Cortical parvalbumin (Pvalb)-expressing neurons provide robust inhibition to neighboring pyramidal neurons, crucial for the proper functioning of cortical networks. This class of inhibitory neurons undergoes extensive synaptic formation and maturation during the first weeks after birth and continue to dynamically maintain their synaptic output throughout adulthood. While several transcription factors, such as Nkx2-1, Lhx6, and Sox6, are known to be necessary for the differentiation of progenitors into Pvalb neurons, which transcriptional programs underlie the postnatal maturation and maintenance of Pvalb neurons' innervation and synaptic function remains largely unknown. Read More

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September 2021

Single-cell analysis at the protein level delineates intracellular signaling dynamic during hematopoiesis.

BMC Biol 2021 Sep 9;19(1):201. Epub 2021 Sep 9.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China.

Background: Hematopoietic stem and progenitor cell (HSPC) subsets in mice have previously been studied using cell surface markers, and more recently single-cell technologies. The recent revolution of single-cell analysis is substantially transforming our understanding of hematopoiesis, confirming the substantial heterogeneity of cells composing the hematopoietic system. While dynamic molecular changes at the DNA/RNA level underlying hematopoiesis have been extensively explored, a broad understanding of single-cell heterogeneity in hematopoietic signaling programs and landscapes, studied at protein level and reflecting post-transcriptional processing, is still lacking. Read More

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September 2021