Cell: Reveals the cell and molecular mechanisms of the development of less protrusion cells in human embryos and the expansion of white matter in the cerebral cortex.

In the course of evolution, the human brain and body ratio increased significantly compared to rodents or non-human primates, providing a neuromaterial basis for increased intelligence and the production of consciousness. !----in terms of the most significant changes in the cerebral cortex, in addition to the rapid expansion of gray matter in the horizontal direction and the formation of a specific folding form of the trench back structure, the volume of the white matter region of the human brain is greatly increased, accompanied by white matter damage has also become a common symptom of epidermis developmental abnormal diseases, serious even leading to cerebral palsy.the small protrusion cells as the most abundant cells in the white matter, forming the myelin that wraps the neuronaamy, promoting the jumping conduction of nerve signals.the study of the development mechanism of protrusion cells can not only help us to better understand the development of the human brain cortex, but also provide the basis for the study of the pathogenesis of white matter injury-related diseases and the exploration of treatment methods.However, due to the rare and limited means of operation of human brain tissue samples, the current research on the development mechanism of small-burst glial cells is mainly based on rodents as a model.considering the huge differences between the human brain and the structure of the mouse brain, it is particularly important to study whether the development of human protrusion cells has a special nature.July 16, 2020, the Arnold Kriegstein Laboratory at the University of California, San Francisco, co-author and co-author, published an online research paper in cell magazine entitled Origins and Proliferative States of The Oligodendrocyte Cell.this work around the origin, proliferation and diffusion of protrusion precursor cells (OPC) during human embryonic development, exploring the cellular and molecular mechanisms of white matter expansion of the human brain.primates have developed a new hair center, the outer subventrve zone (oSVZ), which rodents do not have in the skin.Kriegstein's lab discovered a specialized radiological glial cell, the outer radial glia (oRG), in oSVZ a decade ago, which is essential for the expansion of neurogenesis and the cortex gray matter, and identified the oRG's marker gene five years ago.whether oRG is involved in the occurrence of glial, especially whether oRG can differentiate the production of less protrusion glial cells, academic son has been lacking strong research evidence.reason is that it is difficult to mark and track specific cell types in primates, and oRG is very rare in rodents with genetically modified lines. in this work,, the researchers first used single-cell sequencing and virtual reconstruction to identify a cell differentiation line from oRG to OPC, and discovered a new class of intermediate precursor cells (named Pre-OPC) that mediated differentiation from oRG to OPC.the researchers then histologically dyed the embryonic brain slivers and actually found a large number of oRG, Pre-OPC and OPC in the oSVZ region, as well as transition intermediate cells between the two stem cells.the next researchers directly purified various types of stem cells from fresh clinical tissue samples and performed in vitro differentiation and drug treatment, thus determining that oRG can differentiate to produce Pre-OPC, which further differentiates to produce OPC.finally, the researchers conducted viral markers, cell transplantation, brain culture, and real-time microimaging of immunopuritadized stem cells, observed the dynamic behavior of division and migration of three different types of stem cells, and made two contrasts.a series of experimental results show that primate-specific oRgs can also support glial production, thus providing additional stem cell sources not available to the rodents for the production of human protrusion cells. also corresponds to neurogenesis, and there are intermediate precursor cells in the development of less protrusion cells, unlike the tBR2-positive IPC that has previously been reported to be involved in neurogenesis, which is newly defined pre-OPC for EGFR plus SOX2 plus OLIG2 plus, distributed in oSVZ, and has a special jumping split dynamic behavior (Mitotic Somal Translocation). the two stem cells, oRG and Pre-OPC, which are widely present in the wide oSVZ region, provide sufficient cell sources for the large-scale production of OPC. using real-time microimaging and BrdU analogry, the researchers found that OPC, which has achieved the fate of cells in a relatively long time window (GW20-24), is still able to continuously divide, greatly expanding the stem cell pool and providing a wide range of precursor cells for further differentiation to produce mature protrusion cells and myelin. this is a far cry from previously reported studies in mice that showed resting at OPC during the corresponding developmental period (P0-3) or quickly and eventually differentiated to form protrusion cells after a cycle of cell division. previous reports have shown that the cells produced by stem cell division tend to be dependent on each other in neural developments. classic example is that neurons produced by radial glial (RADIal glia, RG) asymmetric division will climb along its sister RG, while the sub-neurons produced by RG through continuous asymmetrical division will be arranged into cell clones as the cortex aggregates. in real-time microimaging observations of OPC, the researchers found a very interesting phenomenon: the strong rejection between the two sub-cells produced by OPC division, which moved rapidly in the opposite direction. this is significantly different from other types of split cells, including RG and IPC, and may help the rapid diffusion of newborn OPC in the cortex to reduce local concentration and achieve uniform distribution. In order to study the molecular mechanism of mutual repulsion of OPC subcells, the authors compared the genetic expression spectrum differences between OPC and RG and IPC by single-cell sequencing, and found PCDH15, a member of the OPC-specific procalcitasis protein family. the use of RNA interference at RNA level or the use of antibodies at the protein level to block the function of PCDH15, can effectively inhibit the rejection between OPC subcells. further real-time microimaging observations or the results of the division marker protein KI67 staining showed that blocking the rejection behavior of OPC subcells would significantly inhibit the re-division of the sub-oPC. this means that pcDH15 mediated subcellular repellent promotes the effective diffusion and rapid division of OPC. combined with the above findings, these three properties of the less protrusion precursor cells in human embryonic development (additional sources, continuous division, rapid diffusion) will significantly increase the production of small-burst glial cells, thus promoting the expansion of white matter in the cerebral cortex. in the discussion at the end of the article, the authors also cite other specific genes expressed in OPC, other than PCDH15, using single-cell sequencing, which will be studied in the future to deepen understanding of the occurrence of glial matters. , the authors also mention that past studies of abnormal diseases of cerebral cortex tend to focus on neurogenesis, glial development almost as a secondary damage, and the single-cell sequencing results in this paper show that many clinically reported pathogenic genes are not only expressed in neurons, but also have higher transcription levels in glial cells such as OPC, suggesting that glial cells in the occurrence of primary and genetic development of neuropathy. .