A5065475049- Osteoarthritis Treatment and Mechanisms
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Tissue Engineering and Regenerative Medicine
- Full-Duplex Wireless Communications
- Polyomavirus and related diseases
- Plant Virus Research Studies
- Silk-based biomaterials and applications
- Pluripotent Stem Cells Research
- CAR-T cell therapy research
- Congenital heart defects research
- Periodontal Regeneration and Treatments
- Circadian rhythm and melatonin
- Circular RNAs in diseases
- Neuroscience of respiration and sleep
- Immune Cell Function and Interaction
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Electrospun Nanofibers in Biomedical Applications
- Telomeres, Telomerase, and Senescence
- Epigenetics and DNA Methylation
- Bone Tissue Engineering Materials
University of Copenhagen
2020-2024
Sana Biotechnology (United States)
2024
University of Rochester Medical Center
2019-2024
Shriners Hospitals for Children - St. Louis
2016-2020
Duke University
2014-2020
University of Rochester
2019-2020
Shriners Hospitals for Children
2020
Washington University in St. Louis
2016-2019
Duke University Hospital
2016
Duke Medical Center
2016
Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and cells. After CSD, ~11% of CSF proteome altered, up-regulation proteins directly...
Although platelets are the cellular mediators of thrombosis, they also immune cells. Platelets interact both directly and indirectly with cells, impacting their activation differentiation, as well all phases response. Megakaryocytes (Mks) cell source circulating platelets, until recently Mks were typically only considered bone marrow-resident (BM-resident) However, platelet-producing reside in lung, lung express greater levels molecules compared BM Mks. We therefore sought to define...
Significance Engineered replacements for musculoskeletal tissues generally require extensive ex vivo manipulation of stem cells to achieve controlled differentiation and phenotypic stability. The ability control cell using cell-instructive scaffolds that have biomechanical properties approximating those native tissue would represent a transformative advance in functional engineering. goal this study was develop bioactive scaffold capable mediating formation an extracellular matrix with the...
Abstract Competition among adult brain cells has not been extensively researched. To investigate whether healthy glia can outcompete diseased human in the forebrain, we engrafted wild-type (WT) glial progenitor (hGPCs) produced from embryonic stem into striata of mice that had neonatally chimerized with mutant Huntingtin ( mHTT )-expressing hGPCs. The WT hGPCs outcompeted and ultimately eliminated their Huntington’s disease (HD) counterparts, repopulating host glia. Single-cell RNA...
Abstract Human glial progenitor cells (hGPCs) exhibit diminished expansion competence with age, as well after recurrent demyelination. Using RNA-sequencing to compare the gene expression of fetal and adult hGPCs, we identify age-related changes in transcription consistent repression genes enabling mitotic expansion, concurrent onset aging-associated transcriptional programs. Adult hGPCs develop a repressive factor network centered on MYC, regulated by ZNF274, MAX, IKZF3, E2F6. Individual...
ABSTRACT Mesenchymal stem/stromal cells (MSCs) provide an attractive cell source for cartilage repair and therapy; however, the underlying molecular pathways that drive chondrogenesis of these populations adult stem remain poorly understood. We generated a rich data set high‐throughput RNA sequencing human MSCs throughout at 6 different time points. Our consisted 18 libraries with 3 individual donors as biologic replicates, each library possessing depth 100 million reads. Computational...
The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA GRASLND (originally named RNF144A-AS1) as a regulator mesenchymal stem cell (MSC) chondrogenesis. GRASLND, primate-specific lncRNA, is upregulated during MSC chondrogenesis appears to act directly downstream SOX9, but not TGF-β3. We showed that silencing resulted lower accumulation cartilage-like extracellular matrix pellet assay,...
Astrocytic differentiation is developmentally impaired in patients with childhood-onset schizophrenia (SCZ). To determine why, we used genetic gain- and loss-of-function studies to establish the contributions of differentially expressed transcriptional regulators defective glial progenitor cells (GPCs) produced from SCZ patient-derived induced pluripotent (iPSCs). Negative bone morphogenetic protein (BMP) pathway were upregulated GPCs, including BAMBI, FST, GREM1, whose overexpression...
Huntington's disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction hypomyelination. To assess whether a common mechanism might underlie the similar pathology of these otherwise disparate conditions, we used comparative correlation network approaches to analyse RNA-sequencing data from human progenitor cells (hGPCs) produced disease-derived...
Tissue engineering approaches for the repair of osteochondral defects using biomaterial scaffolds and stem cells have remained challenging due to inherent complexities inducing cartilage-like matrix bone-like within same local environment. Members transforming growth factor β (TGFβ) family been extensively utilized in skeletal tissues, but distinct effects on chondrogenic osteogenic differentiation progenitor cells. The goal this study was develop a method direct human bone marrow-derived...
Progressive multifocal leukoencephalopathy is a demyelinating infection of the immunosuppressed brain, mediated by gliotropic polyomavirus JCV. JCV replicates in human glial progenitor cells and astrocytes, which undergo viral T-antigen-triggered mitosis, enabling replication. We asked whether spread might therefore be accelerated proliferation. Using both vitro analysis chimeric mouse model infection, we found that dividing astrocytes supported propagation to substantially greater degree...
ABSTRACT The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines identity mesenchymal progenitors development diversity musculoskeletal tissues they form. Hindlimb has historically been studied with lineage tracing individual genes selected a priori , or at bulk tissue level, which does not allow for determination single cell transcriptional programs yielding mature types tissues. To identify cellular trajectories specification during limb bud...
Abstract Bone marrow-derived mesenchymal stem cells (MSCs) exhibit the potential to undergo chondrogenesis in vitro , forming de novo tissues with a cartilage-like extracellular matrix that is rich glycosaminoglycan and collagen type II. However, it now apparent MSCs comprise an inhomogeneous population of cells, fate individual subpopulations during this differentiation process not well understood. We analyzed trajectory MSC using single cell RNA sequencing (scRNA-seq). Using machine...
Abstract Long non-coding RNAs (lncRNAs) play critical roles in regulating gene expression and cellular processes; however, their musculoskeletal development, disease, regeneration remain poorly understood. Here, we identified a novel lncRNA, Glycosaminoglycan Regulatory ASsociated Non-coDing RNA ( GRASLND ) as regulator of mesenchymal stem cell (MSC) chondrogenesis, investigated its basic molecular mechanism potential application towards regenerative medicine. GRASLND, primate-specific is...
Objectives: Cartilage tissue engineering seeks to provide a functional replacement for damaged or degenerated articular surfaces that develop in osteoarthritis (OA). Human bone marrow-derived mesenchymal stem cells (MSCs) seeded within cartilage-derived matrix (CDM) hemispherical scaffolds exhibit robust chondrogenic differentiation and extracellular (ECM) deposition without evidence of hypertrophic phenotype. However, inflammation an OA joint may inhibit chondrogenesis MSCs induce...
Abstract Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity ability support endochondral ossification. Because it consists tissue, CDM can undergo cellular remodeling, which promote integration with host enables be degraded replaced by neotissue over time. However, enzymatic degradation decellularized tissues occur unpredictably may not allow sufficient time mechanically...
Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection of the immunosuppressed brain, mediated by gliotropic polyomavirus JCV. JCV replicates in human glial progenitor cells and astrocytes, which undergo viral T antigen-triggered mitosis, enabling replication. We asked if spread might therefore be accelerated proliferation. found that dividing astrocytes supported propagation more than mitotically quiescent cells. Both bulk single cell RNA-seq revealed these...
Human glial progenitor cells (hGPCs) emerge during the 2nd trimester to colonize brain, in which a parenchymal pool remains throughout adulthood. While fetal hGPCs are highly migratory and proliferative, their expansion competence diminishes with age, as well following demyelination-associated turnover. To determine basis for decline mobilization capacity, we used bulk single cell RNA-Sequencing compare transcriptional programs of adult hGPCs. We identified age-associated changes gene...