22,783 results match your criteria hescs

GSK3ß inhibitor CHIR 99021 modulates cerebral organoid development through dose-dependent regulation of apoptosis, proliferation, differentiation and migration.

PLoS One 2021 5;16(5):e0251173. Epub 2021 May 5.

Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

Cerebral organoids generated from human pluripotent stem cells (hiPSCs) are unique in their ability to recapitulate human-specific neurodevelopmental events. They are capable of modeling the human brain and its cell composition, including human-specific progenitor cell types; ordered laminar compartments; and both cell-specific transcriptional signatures and the broader telencephalic transcriptional landscape. The serine/threonine kinase, GSK3β, plays a critical role in neurodevelopment, controlling processes as varied as neurogenesis, morphological changes, polarization, and migration. Read More

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Disruption of entire locus leads to embryonic lethality by diminished gene expression and enhanced p53 pathway.

Elife 2021 May 5;10. Epub 2021 May 5.

Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

In vivo function of CDK5 and Abl enzyme substrate 2 (Cables2), belonging to the Cables protein family, is unknown. Here, we found that targeted disruption of the entire locus () caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed disruption of , 50% down-regulation of abutting on the locus, and up-regulation of p53-target genes in gastrulas. Read More

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An Intronic Variant of CHD7 Identified in Autism Patients Interferes with Neuronal Differentiation and Development.

Neurosci Bull 2021 May 4. Epub 2021 May 4.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Read More

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Derivation of Multipotent Neural Progenitors from Human Embryonic Stem Cells for Cell Therapy and Biomedical Applications.

Methods Mol Biol 2021 May 5. Epub 2021 May 5.

Jeffrey Cheah Biomedical Centre, Department of Surgery, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Long-term neuroepithelial-like stem cells (lt-NES) derived from human embryonic stem cells are a stable self-renewing progenitor population with high neurogenic potential and phenotypic plasticity. Lt-NES are amenable to regional patterning toward neurons and glia subtypes and thus represent a valuable source of cells for many biomedical applications. For use in regenerative medicine and cell therapy, lt-NES and their progeny require derivation with high-quality culture conditions suitable for clinical use. Read More

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Novel p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy.

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. Read More

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Endometrial membrane organoids from human embryonic stem cell combined with the 3D Matrigel for endometrium regeneration in asherman syndrome.

Bioact Mater 2021 Nov 16;6(11):3935-3946. Epub 2021 Apr 16.

Key Laboratory of Women's Reproductive Health Research of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310006, China.

Asherman's syndrome (AS), a leading cause of uterine infertility worldwide, is characterized by scarring of the uterine surfaces lacking endometrial epithelial cells, which prevents endometrial regeneration. Current research on cell therapy for AS focuses on mesenchymal and adult stem cells from the endometrium. However, insufficient number, lack of purity, and rapid senescence of endometrial epithelial progenitor cells (EEPCs) during experimental processes restrict their use in cell therapies. Read More

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November 2021

Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice.

Front Med (Lausanne) 2021 15;8:660877. Epub 2021 Apr 15.

Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States.

Islet transplantation can restore glycemic control in patients with type 1 diabetes. Using this procedure, the early stages of engraftment are often crucial to long-term islet function, and outcomes are not always successful. Numerous studies have shown that mesenchymal stem cells (MSCs) facilitate islet graft function. Read More

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Cancer-associated POT1 mutations lead to telomere elongation without induction of a DNA damage response.

EMBO J 2021 May 2:e107346. Epub 2021 May 2.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

Mutations in the shelterin protein POT1 are associated with chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, angiosarcoma, melanoma, and other cancers. These cancer-associated POT1 (caPOT1) mutations are generally heterozygous, missense, or nonsense mutations occurring throughout the POT1 reading frame. Cancers with caPOT1 mutations have elongated telomeres and show increased genomic instability, but which of the two phenotypes promotes tumorigenesis is unclear. Read More

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The case for revisiting Nodal signaling in human pluripotent stem cells.

Stem Cells 2021 May 1. Epub 2021 May 1.

The Jackson Laboratory, Bar Harbor, Maine, USA.

Nodal is a TGF-beta superfamily member that plays a number of critical roles in mammalian embryonic development. Nodal is essential for the support of the peri-implantation epiblast in the mouse embryo, and subsequently acts to specify mesendodermal fate at the time of gastrulation, and later, left-right asymmetry. Maintenance of human pluripotent stem cells (hPSCs) in vitro is dependent on Nodal signaling. Read More

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The chromatin accessibility landscape reveals distinct transcriptional regulation in the induction of human primordial germ cell-like cells from pluripotent stem cells.

Stem Cell Reports 2021 Apr 16. Epub 2021 Apr 16.

Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, China; State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China; Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; National Clinical Research Center for Kidney Disease, Guangzhou, China. Electronic address:

In vitro induction of human primordial germ cell-like cells (hPGCLCs) provides an ideal platform to recapitulate hPGC development. However, the detailed molecular mechanisms regulating the induction of hPGCLCs remain largely uncharacterized. Here, we profiled the chromatin accessibility and transcriptome dynamics throughout the process of hPGCLC induction. Read More

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Human embryonic stem cell classification: random network with autoencoded feature extractor.

J Biomed Opt 2021 Apr;26(5)

University of California-Riverside, Stem Cell Center, Riverside, California, United States.

Significance: Automated understanding of human embryonic stem cell (hESC) videos is essential for the quantified analysis and classification of various states of hESCs and their health for diverse applications in regenerative medicine.

Aim: This paper aims to develop an ensemble method and bagging of deep learning classifiers as a model for hESC classification on a video dataset collected using a phase contrast microscope.

Approach: The paper describes a deep learning-based random network (RandNet) with an autoencoded feature extractor for the classification of hESCs into six different classes, namely, (1) cell clusters, (2) debris, (3) unattached cells, (4) attached cells, (5) dynamically blebbing cells, and (6) apoptotically blebbing cells. Read More

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Generation of biologically active recombinant human OCT4 protein from .

3 Biotech 2021 May 8;11(5):207. Epub 2021 Apr 8.

Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039 Assam India.

Octamer-binding transcription factor 4 (OCT4) is vital for early embryonic development and is a master regulator of pluripotency in embryonic stem cells. Notably, OCT4 is a key reprogramming factor to derive induced pluripotent stem cells, which have tremendous prospects in regenerative medicine. In the current study, we report heterologous expression and purification of human OCT4 in to produce pure recombinant protein under native conditions. Read More

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Towards physiologically relevant human pluripotent stem cell (hPSC) models of Parkinson's disease.

Stem Cell Res Ther 2021 Apr 29;12(1):253. Epub 2021 Apr 29.

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, US.

The derivation of human embryonic stem cells followed by the discovery of induced pluripotent stem cells and leaps in genome editing approaches have continuously fueled enthusiasm for the development of new models of neurodegenerative diseases such as Parkinson's disease (PD). PD is characterized by the relative selective loss of dopaminergic neurons (DNs) in specific areas of substantia nigra pars compacta (SNpc). While degeneration in late stages can be widespread, there is stereotypic early degeneration of these uniquely vulnerable neurons. Read More

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From Stem Cells to Bone-Forming Cells.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Department of Molecular Medicine, Sapienza University of Rome, Viale Regina 324, 00161 Rome, Italy.

Bone formation starts near the end of the embryonic stage of development and continues throughout life during bone modeling and growth, remodeling, and when needed, regeneration. Bone-forming cells, traditionally termed osteoblasts, produce, assemble, and control the mineralization of the type I collagen-enriched bone matrix while participating in the regulation of other cell processes, such as osteoclastogenesis, and metabolic activities, such as phosphate homeostasis. Osteoblasts are generated by different cohorts of skeletal stem cells that arise from different embryonic specifications, which operate in the pre-natal and/or adult skeleton under the control of multiple regulators. Read More

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Rejuvenated Stem/Progenitor Cells for Cartilage Repair Using the Pluripotent Stem Cell Technology.

Bioengineering (Basel) 2021 Apr 10;8(4). Epub 2021 Apr 10.

Steadman Philippon Research Institute, Vail, CO 81657, USA.

It is widely accepted that chondral defects in articular cartilage of adult joints are never repaired spontaneously, which is considered to be one of the major causes of age-related degenerative joint disorders, such as osteoarthritis. Since mobilization of subchondral bone (marrow) cells and addition of chondrocytes or mesenchymal stromal cells into full-thickness defects show some degrees of repair, the lack of self-repair activity in adult articular cartilage can be attributed to lack of reparative cells in adult joints. In contrast, during a fetal or embryonic stage, joint articular cartilage has a scar-less repair activity, suggesting that embryonic joints may contain cells responsible for such activity, which can be chondrocytes, chondroprogenitors, or other cell types such as skeletal stem cells. Read More

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Differential Expression of the Tetraspanin CD9 in Normal and Leukemic Stem Cells.

Biology (Basel) 2021 Apr 8;10(4). Epub 2021 Apr 8.

Institut de Recherche en Hématologie et Transplantation (IRHT), Hôpital du Hasenrain, 87 Avenue d'Altkirch, 68100 Mulhouse, France.

CD9 plays a crucial role in cellular growth, mobility, and signal transduction, as well as in hematological malignancy. In myeloid neoplasms, CD9 is involved in the altered interactions between leukemic and stromal cells. However, apart from its role in CD34 progenitors and myeloid and megakaryocytic differentiation, its function in normal and leukemic pluripotent cells has not yet been determined. Read More

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Principles of signaling pathway modulation for enhancing human naive pluripotency induction.

Cell Stem Cell 2021 Apr 23. Epub 2021 Apr 23.

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address:

Isolating human MEK/ERK signaling-independent pluripotent stem cells (PSCs) with naive pluripotency characteristics while maintaining differentiation competence and (epi)genetic integrity remains challenging. Here, we engineer reporter systems that allow the screening for defined conditions that induce molecular and functional features of human naive pluripotency. Synergistic inhibition of WNT/β-CATENIN, protein kinase C (PKC), and SRC signaling consolidates the induction of teratoma-competent naive human PSCs, with the capacity to differentiate into trophoblast stem cells (TSCs) and extraembryonic naive endodermal (nEND) cells in vitro. Read More

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Maturation conditions, post-ovulatory age, medium pH, and ER stress affect [Ca]i oscillation patterns in mouse oocytes.

J Assist Reprod Genet 2021 Apr 29. Epub 2021 Apr 29.

Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510000, China.

Insufficiency of oocyte activation impairs the subsequent embryo development in assisted reproductive technology (ART). Intracellular Ca concentration ([Ca]i) oscillations switch the oocytes to resume the second meiosis and initiate embryonic development. However, the [Ca]i oscillation patterns in oocytes are poorly characterized. Read More

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Testicular germ cell tumors arise in the absence of sex-specific differentiation.

Development 2021 May 26;148(9). Epub 2021 Apr 26.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

In response to signals from the embryonic testis, the germ cell intrinsic factor NANOS2 coordinates a transcriptional program necessary for the differentiation of pluripotent-like primordial germ cells toward a unipotent spermatogonial stem cell fate. Emerging evidence indicates that genetic risk factors contribute to testicular germ cell tumor initiation by disrupting sex-specific differentiation. Here, using the 129. Read More

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NB-UVB Induces Melanocytic Differentiation of Human Hair Follicle Neural Crest Stem Cells.

Ann Dermatol 2020 Aug 30;32(4):289-297. Epub 2020 Jun 30.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Phototherapy is an important method to treat vitiligo. However, it is unclear how phototherapy affects melanocyte precursors and skin neural crest stem cells.

Objective: To investigate the underlying mechanisms of narrow-band ultraviolet B (NB-UVB) induced melanocyte lineage differentiated from human scalp-derived neural crest stem cells (HS-NCSCs). Read More

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Detection of the residual concentration of sodium dodecyl sulfate in the decellularized whole rabbit kidney extracellular matrix.

Cell Tissue Bank 2021 Apr 28. Epub 2021 Apr 28.

Pediatric Urology and Regenerative Medicine Research Center, Pediatric Center of Excellence, Department of Pediatric Urology, Children's Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Gharibs Street, Keshavarz Boulevard, 1419733151, Tehran, Iran.

To optimize rabbit kidney decellularization protocol, using sodium dodecyl sulfate (SDS) as a commonly used detergent, a methylene blue based assay was employed for detecting the minimum nontoxic SDS level for future cell seeding. The rabbit kidney tissues were decellularized with the perfusion-based method and underwent several investigations to determine the efficacy of decellularization in preserving the extracellular matrix (ECM) and cell removal. SDS detection was performed by incubating with methylene blue and subsequent extraction with chloroform. Read More

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Identification of candidate PAX2-regulated genes implicated in human kidney development.

Sci Rep 2021 Apr 27;11(1):9123. Epub 2021 Apr 27.

Department of Nephrology and Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.

PAX2 is a transcription factor essential for kidney development and the main causative gene for renal coloboma syndrome (RCS). The mechanisms of PAX2 action during kidney development have been evaluated in mice but not in humans. This is a critical gap in knowledge since important differences have been reported in kidney development in the two species. Read More

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Generation of 3D Whole Lung Organoids from Induced Pluripotent Stem Cells for Modeling Lung Developmental Biology and Disease.

J Vis Exp 2021 Apr 12(170). Epub 2021 Apr 12.

Department of Pediatrics, University of California, San Diego School of Medicine; Sanford Consortium for Regenerative Medicine; Sanford Burnham Prebys Medical Discovery Institute.

Human lung development and disease has been difficult to study due to the lack of biologically relevant in vitro model systems. Human induced pluripotent stem cells (hiPSCs) can be differentiated stepwise into 3D multicellular lung organoids, made of both epithelial and mesenchymal cell populations. We recapitulate embryonic developmental cues by temporally introducing a variety of growth factors and small molecules to efficiently generate definitive endoderm, anterior foregut endoderm, and subsequently lung progenitor cells. Read More

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Modeling human retinoblastoma using embryonic stem cell-derived retinal organoids.

STAR Protoc 2021 Jun 7;2(2):100444. Epub 2021 Apr 7.

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.

Retinoblastoma (Rb) is the most prevalent intraocular malignancy in early childhood. Traditional models are unable to accurately recapitulate the origin and development of human Rb. Here, we present a protocol to establish a novel human Rb organoid (hRBO) model derived from genetically engineered human embryonic stem cells (hESCs). Read More

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Prenatal Development and Function of Human Mononuclear Phagocytes.

Front Cell Dev Biol 2021 8;9:649937. Epub 2021 Apr 8.

Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

The human mononuclear phagocyte (MP) system, which includes dendritic cells, monocytes, and macrophages, is a critical regulator of innate and adaptive immune responses. During embryonic development, MPs derive sequentially in yolk sac progenitors, fetal liver, and bone marrow haematopoietic stem cells. MPs maintain tissue homeostasis and confer protective immunity in post-natal life. Read More

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From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell-based Embryo Models along the Embryonic Timeline.

Adv Sci (Weinh) 2021 Apr 2;8(8):2004250. Epub 2021 Mar 2.

Maastricht University Universiteitssingel 40 Maastricht 6229 ER The Netherlands.

In recent years, stem cell-based models that reconstruct mouse and human embryogenesis have gained significant traction due to their near-physiological similarity to natural embryos. Embryo models can be generated in large numbers, provide accessibility to a variety of experimental tools such as genetic and chemical manipulation, and confer compatibility with automated readouts, which permits exciting experimental avenues for exploring the genetic and molecular principles of self-organization, development, and disease. However, the current embryo models recapitulate only snapshots within the continuum of embryonic development, allowing the progression of the embryonic tissues along a specific direction. Read More

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miR-375 Promotes Pancreatic Differentiation by Affecting Different Target Genes at Different Stages.

Stem Cells Int 2021 7;2021:6642983. Epub 2021 Apr 7.

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.

Human embryonic stem cells (hESCs) possess the ability to differentiate into insulin-producing cells (IPCs), which can be used to treat type I diabetes. miR-375 is an essential transcriptional regulator in the development and maturation of the pancreas. In this study, we optimized a protocol to differentiate hESCs into IPCs and successfully obtained IPCs. Read More

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Functions and mechanisms of circular RNAs in regulating stem cell differentiation.

RNA Biol 2021 Apr 26:1-14. Epub 2021 Apr 26.

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Stem cells are a class of undifferentiated cells with great self-renewal and differentiation capabilities that can differentiate into mature cells in specific tissue types. Stem cell differentiation plays critical roles in body homoeostasis, injury repair and tissue generation. The important functions of stem cell differentiation have resulted in numerous studies focusing on the complex molecular mechanisms and various signalling pathways controlling stem cell differentiation. Read More

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CXCL13 promotes intestinal tumorigenesis through the activation of epithelial AKT signaling.

Cancer Lett 2021 Apr 22;511:1-14. Epub 2021 Apr 22.

Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China. Electronic address:

The excessive release of proinflammatory chemokines promotes cell proliferation and tumor growth in colorectal cancer. However, their regulatory functions and molecular pathogenesis have not been well elucidated. Here, we observed the upregulation of chemokine (C-X-C motif) ligand 13 (CXCL13) in human colorectal cancers and mouse intestinal tumors. Read More

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A fetal wave of human type 3 effector γδ cells with restricted TCR diversity persists into adulthood.

Sci Immunol 2021 Apr;6(58)

Institute of Immunology, Hannover Medical School (MHH), Hannover, Germany.

Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector γδ T cells. However, it is unclear whether this process occurs similarly in humans and whether it comprises a dedicated subset of innate-like type 3 effector γδ T cells. Here, we present a protocol for high-throughput sequencing of and pairs that comprise the clonal γδTCR. Read More

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