Marcus May

Bio: Marcus May is an academic researcher from Ruhr University Bochum. The author has contributed to research in topics: Neural stem cell & Progenitor cell. The author has an hindex of 2, co-authored 2 publications receiving 9 citations.

Cell tracking in vitro reveals that the extracellular matrix glycoprotein Tenascin-C modulates cell cycle length and differentiation in neural stem/progenitor cells of the developing mouse spinal cord.

Abstract: Generation of astrocytes during the development of the mammalian spinal cord is poorly understood. Previously, we have shown that the glycoprotein of the extracellular matrix (ECM) tenascin-C (Tnc) modulates the expression territories of the patterning genes Nkx6.1 and Nkx2.2 in the developing ventral spinal cord, tunes the responsiveness of neural stem/progenitor cells towards the cytokines FGF2 and EGF and thereby promotes astrocyte maturation. In order to obtain further mechanistic insight into these processes, we have compared embryonic day-15 spinal cord neural progenitor cells (NPCs) from wild-type and Tnc knockout mice using continuous single-cell live imaging and cell lineage analysis in vitro. Tnc knockout cells displayed a significantly reduced rate of cell division both in response to FGF2 and EGF. When individual clones of dividing cells were investigated with regard to their cell lineage trees using the tTt tracking software, it appeared that the cell cycle length in response to growth factors was reduced in the knockout. Furthermore, when Tnc knockout NPCs were induced to differentiate by the removal of FGF2 and EGF glial differentiation was enhanced. We conclude that the constituent of the stem cell niche Tnc contributes to preserve stemness of NPCs.

Sulfation of Glycosaminoglycans Modulates the Cell Cycle of Embryonic Mouse Spinal Cord Neural Stem Cells.

Abstract: In the developing spinal cord neural stem and progenitor cells (NSPCs) secrete and are surrounded by extracellular matrix (ECM) molecules that influence their lineage decisions. The chondroitin sulfate proteoglycan (CSPG) DSD-1-PG is an isoform of receptor protein tyrosine phosphatase-beta/zeta (RPTPb/z), a trans-membrane receptor expressed by NSPCs. The chondroitin sulfate glycosaminoglycan chains are sulfated at distinct positions by sulfotransferases, thereby generating the distinct DSD-1-epitope that is recognized by the monoclonal antibody (mAb) 473HD. We detected the epitope, the critical enzymes and RPTPb/z in the developing spinal cord. To obtain insight into potential biological functions, we exposed spinal cord NSPCs to sodium chlorate. The reagent suppresses the sulfation of glycosaminoglycans, thereby erasing any sulfation code expressed by the glycosaminoglycan polymers. When NSPCs were treated with chlorate and cultivated in the presence of FGF2, their proliferation rate was clearly reduced, while NSPCs exposed to EGF were less affected. Time-lapse video microscopy and subsequent single-cell tracking revealed that pedigrees of NSPCs cultivated with FGF2 were strongly disrupted when sulfation was suppressed. Furthermore, the NSPCs displayed a protracted cell cycle length. We conclude that the inhibition of sulfation with sodium chlorate interferes with the FGF2-dependent cell cycle progression in spinal cord NSPCs.

The Unifying Hypothesis of Alzheimer’s Disease: Heparan Sulfate Proteoglycans/Glycosaminoglycans Are Key as First Hypothesized Over 30 Years Ago

Abstract: The updated "Unifying Hypothesis of Alzheimer's disease" (AD) is described that links all the observed neuropathology in AD brain (i.e., plaques, tangles, and cerebrovascular amyloid deposits), as well as inflammation, genetic factors (involving ApoE), "AD-in-a-Dish" studies, beta-amyloid protein (Aβ) as a microbial peptide; and theories that bacteria, gut microflora, gingivitis and viruses all play a role in the cause of AD. The common link is the early accumulation of heparan sulfate proteoglycans (HSPGs) and heparan sulfate glycosaminoglycans (GAGs). HS GAG accumulation and/or decreased HS GAG degradation is postulated to be the key initiating event. HS GAGs and highly sulfated macromolecules induce Aβ 1-40 (but not 1-42) to form spherical congophilic maltese-cross star-like amyloid core deposits identical to those in the AD brain. Heparin/HS also induces tau protein to form paired helical filaments (PHFs). Increased sulfation and/or decreased degradation of HSPGs and HS GAGs that occur due to brain aging leads to the formation of plaques and tangles in AD brain. Knockout of HS genes markedly reduce the accumulation of Aβ fibrils in the brain demonstrating that HS GAGs are key. Bacteria and viruses all use cell surface HS GAGs for entry into cells, including SARS-CoV-2. Bacteria and viruses cause HS GAGs to rapidly increase to cause near-immediate aggregation of Aβ fibrils. "AD-in-a-dish" studies use "Matrigel" as the underlying scaffold that spontaneously causes plaque, and then tangle formation in a dish. Matrigel mostly contains large amounts of perlecan, the same specific HSPG implicated in AD and amyloid disorders. Mucopolysaccharidoses caused by lack of specific HS GAG enzymes lead to massive accumulation of HS in lysosomal compartments in neurons and contribute to cognitive impairment in children. Neurons full of HS demonstrate marked accumulation and fibrillization of Aβ, tau, α-synuclein, and prion protein (PrP) in mucopolysaccharidosis animal models demonstrating that HS GAG accumulation is a precursor to Aβ accumulation in neurons. Brain aging leads to changes in HSPGs, including newly identified splice variants leading to increased HS GAG sulfation in the AD brain. All of these events lead to the new "Unifying Hypothesis of Alzheimer's disease" that further implicates HSPGs /HS GAGs as key (as first hypothesized by Snow and Wight in 1989).

Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration

Abstract: Stem cells maintain a subtle balance between self-renew and differentiate under the regulatory network supported by both intracellular and extracellular components. Proteoglycans are large glycoproteins presented abundantly on the cell surface and in the extracellular matrix where they play pivotal roles in facilitating signaling transduction and maintaining stem cell homeostasis. In this review, we outlined the distinct proteoglycans profiles and their functions in the regulation of stem cell homeostasis, as well as recent progresses and prospects of utilizing proteoglycans /glycosaminoglycans as a novel glycomics carrier or bio-active molecules in bone regeneration.