Lineage Tracing and Cell Potential of Postnatal Single Progenitor Cells In Vivo

Abstract

SummaryUnderstanding the contribution of adult neural progenitor cells (NPCs) and their lineage potential is a great challenge in neuroscience. To reveal progenitor diversity and cell-lineage relationships of postnatal NPCs in the subventricular zone (SVZ), we performed in vivo lineage-tracing genetic analysis using the UbC-StarTrack. We determined the progeny of single SVZ-NPCs, the number of cells per clone, the dispersion of sibling cells, and the cell types within clones. Long-term analysis revealed that both the cell-dispersion pattern and number of cells comprising clones varied depending on the glial/neuronal nature of sibling cells. Sibling-olfactory interneurons were primarily located within the same layer, while sibling-glial cells populated SVZ-adjacent areas. Sibling astrocytes and interneurons did not form big clones, whereas oligodendroglial-lineage clones comprised the largest clones originated in adult brains. These results demonstrate the existence of SVZ postnatal bipotential progenitors that give rise to clones widely dispersed across the olfactory bulb and SVZ-adjacent areas.

Cell Progeny in the Olfactory Bulb after Targeting Specific Progenitors with Different UbC-StarTrack Approaches

“…Specific progenitor cells were targeted at E12 to track their adult cell progeny in the OB. StarTrack is a powerful tool to examine the fate and the clonal relationship between cells derived from specific progenitors in vivo, under both physiological and pathological conditions [15][16][17]21,25,[27][28][29][30][31][32][33]. This tool also allows progenitor cells to be tracked in vivo, avoiding genetic manipulation of the animals or viral injections.…”

“…The past two decades have witnessed an accumulation of abundant evidence regarding such heterogeneity, not only in the OB, but also in the dorsal cortex [39], hippocampus [40], and cerebellum [30]. Moreover, recent data show the bipotent capacity of postnatal NSCs to generate OB interneurons and glia in the cortex and striatum [21]. NSCs generating OB cells follow highly patterned and complex behavior during embryogenesis [41,42], and at post-natal stages [13,41].…”

“…The sections were examined under an epifluorescence microscope (Eclipse E600; Nikon Instruments, Melville, NY, USA), equipped with GFP (FF01-473/10), mCherry (FF01-590/20) and Cy5 (FF01-540/15) filters. Images were then acquired on a TCS-SP5 confocal microscope (Leica Microsystems, Wetzlar, Germany) using a 20x objective (Leica), with the wavelength conformation as described previously (Table 2) [17,21]. Confocal laser lines were maximal around 40% in all samples.…”

“…In the embryo, glial progenitor cells are located in the most rostral part of the lateral ventricle (LV), which corresponds to the olfactory ventricle (OV) [15][16][17]. This complex organization and connectivity of the cells that populate the OB are largely determined during embryonic development [5,18,19], albeit with an additional contribution postnatally [20,21]. To date, different approaches have been used to assess the diversity of OB progenitor pools during development, including the use of fluorescent and lipophilic tracers, viral vectors, immunostaining, and the generation of specific mouse lines.…”

Early lineage segregation of the retinal basal glia in the Drosophila eye disc

“…In vertebrates, in vivo lineage tracing of single genetically marked neural progenitor cells (NPC) showed that some NPCs generate both neurons and glia, while other NPCs generate only specific glia types (astrocytes or oligodendrocytes) or only neurons 48 . There is no example that one type of glia derives from another type of glia.…”