Andrew Ho

Paris Diderot University | UP7 · Pathophysiology of striated muscles

The proper regulation of muscle stem cell (MuSC) fate by cues from the niche is essential for regeneration of skeletal muscle. How pro-regenerative niche factors control the dynamics of MuSC fate decisions remains unknown due to limitations of population-level endpoint assays. To address this knowledge gap, we developed a novel binary dynamic fluor...

The molecular mechanisms underlying lineage commitment of stem and progenitor cells have implications for deriving specific cell types in vitro for regenerative medicine purposes. Current approaches to derive transfusable amounts of erythrocytes and platelets fall short of producing physiologically relevant amounts of each cell type. Thrombopoietin...

Treatments are lacking for sarcopenia, a debilitating age-related skeletal muscle wasting syndrome. Here we identify elevated 15-PGDH, the Prostaglandin E2 (PGE2)–degrading enzyme, as a hallmark of aged tissues, including skeletal muscle. The resulting reduction in PGE2 signaling is a major contributor to muscle atrophy in aged mice and results fro...

The molecular mechanisms underlying lineage commitment of stem and progenitor cells have implications for deriving specific cell types in vitro for regenerative medicine purposes and elucidating the aberrant pathways responsible for pathological conditions. We investigated Megakaryocytic-Erythroid Progenitors (MEP) commitment to the megakaryocytic...

In the version of this Article originally published, the name of author Andrew Tri Van Ho was coded wrongly, resulting in it being incorrect when exported to citation databases. This has been corrected, though no visible changes will be apparent.

The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identi...

The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identi...

To overcome the finite supply of muscle stem cells available for cell therapy, a study now describes a strategy for obtaining an unlimited source of myogenic progenitors derived from human pluripotent cells. Two neuronal cell surface receptors facilitate the selection of a population with enhanced regenerative potential.

Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets...

Muscle regeneration is a dynamic process during which cell state and identity change over time. A major roadblock has been a lack of tools to resolve a myogenic progression in vivo. Here we capitalize on a transformative technology, single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell and previously unrecognized progeni...

Muscle stem cells play a central role in muscle regeneration. Most studies in the field of muscle regeneration focus on the unraveling of muscle stem cell biology to devise strategies for treating failing muscles as seen in aging and muscle-related diseases. However, the common method used in assessing stem cell function in vivo is laborious, as it...

Skeletal muscle mass, function, and repair capacity all progressively decline with aging, restricting mobility, voluntary function, and quality of life. Skeletal muscle repair is facilitated by a population of dedicated muscle stem cells (MuSCs), also known as satellite cells, that reside in anatomically defined niches within muscle tissues. In adu...

To test if proteolysis is involved in tumor cell extravasation, we developed an in vitro model where tumor cells cross an endothelial monolayer cultured on a basement membrane. Using this model we classified the ability of the cells to transmigrate through the endothelial cell barrier onto the underlying matrix, and scored this invasion according t...

Coordinating the balance between progenitor self-renewal and myogenic differentiation is required for a regulated expansion of the developing muscles. Previous observation that neural crest cells (NCCs) migrate throughout the somite regions, where trunk skeletal muscles first emerge, suggests a potential role for these cells in influencing early mu...

Vascular calcifications can occur in the elderly and in patients suffering from various diseases. Interestingly, depending on the pathology, different regions of the arterial system can be affected. Embryonic observations have clearly indicated that vascular smooth muscle cell (VSMC) origin is notably heterogeneous. For instance, in the aorta, VSMC...

Twitching Ad.cre transduced RbΔf:p107−/− myotubes under hypoxia. Rbf/f:p107−/− myoblasts were transduced with Ad.cre, induced to differentiate after 48 hr, transferred to hypoxia and video captured at DM-5. (SWF)

Twitching wild-type myotubes treated with 3-MA. Control wild-type myoblasts were induced to differentiate and treated with 3-MA and video captured at DM-5. (SWF)

Twitching mgRb:Rb−/−:p130−/− myotubes treated with 3-MA. mgRb:Rb−/−:p130−/− myoblasts were induced to differentiate and treated with 3-MA and video captured at DM-5. (SWF)

A rare TKO myotube containing 3 nuclei. Immunostaining for pRb (green) of Ad.EV and Ad.cre transduced Rbf/f:p107−/−:p130−/− cultures at DM-2. Top row, low exposure images demonstrating absence of detectable pRb in Ad.cre transduced culture. Bottom row, high exposure images to highlight a short myotube containing 3 nuclei, which is devoid of detecta...

Twitching Ad.cre transduced RbΔf myotubes under hypoxia. Rbf/f myoblasts were transduced with Ad.cre, induced to differentiate after 48 hr, transferred to hypoxia and video captured at DM-5. (SWF)

Twitching Ad.cre transduced RbΔf:p130−/− myotubes under hypoxia. Rbf/f:p130−/− myoblasts were transduced with Ad.cre, induced to differentiate after 48 hr, transferred to hypoxia and video captured at DM-5. (SWF)

Twitching Ad.cre transduced RbΔf:p107−/−:p130−/− myotube/myocyte under hypoxia. Rbf/f:p107−/−:p130−/− myoblasts were transduced with Ad.cre, induced to differentiate after 48 hr, transferred to hypoxia and video captured at DM-5. (SWF)

The tumor suppressor Rb is thought to control cell proliferation, survival and differentiation. We recently showed that differentiating Rb-deficient mouse myoblasts can fuse to form short myotubes that quickly collapse through a mechanism involving autophagy, and that autophagy inhibitors or hypoxia could rescue the defect leading to long, twitchin...

The current model for the intrinsic apoptotic pathway holds that mitochondrial activation of caspases in response to cytotoxic drugs requires both Apaf-1-induced dimerization of procaspase 9 and Smac/Diablo-mediated sequestration of inhibitors of apoptosis proteins (IAPs). Here, we showed that either pathway can independently promote caspase 9 acti...

Assembly of the apoptosome in response to mitochondrial permeabilization, the hallmark of the intrinsic apoptotic pathway, involves binding of cytochrome c to Apaf1, recruitment and auto-processing of the apical/signaling pro-caspase-9, and coupled activation of downstream/executioner caspases like caspase 3. Evidence now indicates that certain apo...

Inactivation of the tumor suppressor Rb in the mouse induces cell death, which depends entirely (in lens, CNS) and only partly (PNS, skeletal muscles) on Apaf1/Ced4, an apoptosomal factor thought to be required for processing procaspase-9 following mitochondrial permeabilization. Here, we report that in response to cytotoxic drugs, Apaf1(-/-) prima...

Increased pericellular proteolysis due to an imbalance between MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of metalloproteinases) promotes early stages of tumorigenesis. We have reported that TIMP-1 down-regulation confers tumorigenicity on immortal Swiss 3T3 fibroblasts. In pursuit of the mechanism involved in this transformation...

Female reproductive tissues possess a unique ability to accommodate a remarkable amount of cell turnover and extracellular matrix (ECM) remodeling following puberty. Cellular structures within ovary, uterus, and mammary tissue not only change cyclically in response to ovarian hormones but also undergo differentiation during pregnancy, and eventuall...

Tissue inhibitors of metalloproteinases (TIMP) block proteolytic degradation of extracellular matrix and consequently impede tumor invasion and metastasis. In addition, we have previously reported that hepatic TIMP-1 modulation alters the susceptibility of the liver to oncogene (simian virus 40 T-antigen; TAg)-induced tumorigenesis in a double-tran...

Within the tumor-stromal microenvironment a disrupted balance between matrix metalloproteinases (MMPs) and their inhibitors compromises the integrity of the extracellular matrix and promotes malignancy. Tissue inhibitors of metalloproteinases (TIMPs) have been linked to tumor suppression in studies of genetically altered tissue culture cells and in...

Thesis (M.Sc.)--University of Toronto, 2000. Includes bibliographical references.