A5030798882- Muscle Physiology and Disorders
- Mesenchymal stem cell research
- Hematopoietic Stem Cell Transplantation
- Pluripotent Stem Cells Research
- Genetics, Aging, and Longevity in Model Organisms
- Tissue Engineering and Regenerative Medicine
- Immune Cell Function and Interaction
- Adipose Tissue and Metabolism
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Sarcoma Diagnosis and Treatment
- GDF15 and Related Biomarkers
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Pancreatic function and diabetes
- Wound Healing and Treatments
- RNA Research and Splicing
- Zebrafish Biomedical Research Applications
Harvard University
2016-2025
Joslin Diabetes Center
2016-2025
Stanford University
2001-2025
Harvard Stem Cell Institute
2016-2025
Harvard University Press
2015-2025
Cell Medica (Switzerland)
2024
Howard Hughes Medical Institute
2010-2016
Beth Israel Deaconess Medical Center
2016
Brigham and Women's Hospital
2006-2016
San Francisco General Hospital
2016
To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, GFP+:GFP- parabiotic mice, found...
Loss of immune function and an increased incidence myeloid leukemia are two the most clinically significant consequences aging hematopoietic system. To better understand mechanisms underlying aging, we evaluated cell intrinsic functional molecular properties highly purified long-term stem cells (LT-HSCs) from young old mice. We found that LT-HSC was accompanied by autonomous changes, including self-renewal, differential capacity to generate committed lymphoid progenitors, diminished...
Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration Duchenne muscular dystrophy (DMD). Removing one or more exons from mutated transcript can produce an in-frame mRNA a truncated, but still functional, protein. In this study, we developed tested direct gene-editing approach to induce exon deletion recover dystrophin expression mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) clustered regularly...
In the adult central nervous system, vasculature of neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline neurogenesis cognitive function is associated with reduced blood flow decreased numbers cells. Therefore, restoring functionality should counteract some negative effects aging. We show that factors found in young induce vascular remodeling, culminating increased improved olfactory discrimination aging mice. Further, we...
Hematopoietic stem cells (HSCs) reside predominantly in bone marrow, but low numbers of HSCs are also found peripheral blood. We examined the fate blood-borne using genetically marked parabiotic mice, which surgically conjoined and share a common circulation. Parabionts rapidly established stable, functional cross engraftment partner-derived maintained hematopoiesis after surgical separation. Determination residence time injected progenitor suggests that circulating HSCs/progenitors cleared...
Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting blood contains humoral "rejuvenating" factors can restore regenerative function. Here, we demonstrate the circulating protein growth differentiation factor 11 (GDF11) rejuvenating for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, heterochronic parabiosis or delivery recombinant protein, reversed functional...
Both intrinsic cell state changes and variations in the composition of stem populations have been implicated as contributors to aging. We used single-cell RNA-seq dissect variability hematopoietic (HSC) progenitor from young old mice two strains. found that cycle dominates within each population there is a lower frequency cells G1 phase among compared with long-term HSCs, suggesting they traverse through faster. Moreover, transcriptional HSCs during aging are inversely related those upon HSC...
Knowledge of the molecular networks controlling proliferation and fate hematopoietic stem cells (HSC) is essential to understand their function in maintaining blood cell production during normal hematopoiesis upon clinical transplantation. Using highly purified progenitor populations, we define index status cycle machinery at discrete stages differentiation cytokine-mediated HSC mobilization. We identify distinct sets proteins that specifically associate with differentiation, self-renewal,...