Abstract
Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any possible aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations, and their progenitors, is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS), oligodendrocytes (OLs) are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering the complexity of human OL identity.
Highlights
One of the main challenges of modern neurobiology is discovering how cellular diversity in the brain emerges during development
Within the neocortical gray matter, the scenario is even more compelling, as suggested by a very recent paper from the laboratory of Paola Arlotta, in which we have shown that while Pdgfrα+ oligodendrocyte progenitor cells (OPCs) populate all layers of the neocortex, their ability to generate mature APC+/Plp1+ OLs is dependent on their laminar position within the neocortex; the amount of myelin found in the superficial layers is dramatically lower as compared to the deep layers (Tomassy et al, 2014; Figure 2)
We showed that the layer-specific ability of neocortical OPCs to give rise to myelinating OLs is affected by the neuronal subtype present in their immediate proximity
Summary
How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses. Among all glial cells of the central nervous system (CNS), oligodendrocytes (OLs) are a specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. We will try to address some specific questions: do multiple OL subtypes exist in the CNS?
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