Studies

To understand how cells communicate with each other, it is essential to define the cellular secretome, a collection of proteins including soluble secreted, unconventionally secreted and proteolytically-shed proteins. Quantitative methodologies to decipher the secretome are challenging, due to the requirement of large cell numbers and abundant serum proteins that interfere with the detection of low-abundant cellular secretome proteins. Here, we miniaturized secretome analysis by developing the ...

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related ...

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related ...

Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder mainly caused by autosomal recessive mutations in Npc1 which result in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is one of the prominent pathological features, consequences of NPC1 loss on microglial function and disease outcome remain largely unknown. Here, we provide an in-depth characterization of microglial proteomic signatures and phenotypes in an NPC1-deficient (Npc1-/-) murine model. We ...

Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin ...

Oligodendrocytes extend numerous cellular processes that wrap multiple times around axons to generate lipid-rich myelin sheaths. Myelin biogenesis requires an enormously productive biosynthetic machinery for generating and delivering these large amounts of newly synthesized lipids. Yet, a complete understanding of this process remains elusive. Utilizing volume electron microscopy, we demonstrate that the oligodendroglial endoplasmic reticulum (ER) is enriched in developing myelin, extending into ...