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

2021

Cells

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During embryonic development, progenitor cells are progressively restricted in their potential to generate different neural cells. A specific progenitor cell type, the radial glial cells, divides symmetrically and then asymmetrically to produce neurons, astrocytes, oligodendrocytes, and NG2-glia in the cerebral cortex. However, the potential of individual progenitors to form glial lineages remains poorly understood. To further investigate the cell progeny of single pallial GFAP-expressing progenitors, we used the in vivo genetic lineage-tracing method, the UbC-(GFAP-PB)-StarTrack. After targeting those progenitors in embryonic mice brains, we tracked their adult glial progeny in lower cortical layers. Clonal analyses revealed the presence of clones containing sibling cells of either a glial cell type (uniform clones) or two different glial cell types (mixed clones). Further, the clonal size and rostro-caudal cell dispersion of sibling cells differed depending on the cell type. We concluded that pallial E14 neural progenitors are a heterogeneous cell population with respect to which glial cell type they produce, as well as the clonal size of their cell progeny.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gliogenic Potential of Single Pallial Radial Glial Cells in Lower Cortical Layers

Ojalvo-Sanz

2021

Cells

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“…Here, using the UbC-(NG2-PB)-StarTrack, we show that embryonic NG2-progenitors sited in the pallium give rise to different glial cell types but also some neurons. In addition, NG2-progenitors also give rise to interneurons located at different layers of the adult olfactory bulb 41 .…”

Section: Discussionmentioning

confidence: 99%

Cell Fate Potential of NG2 Progenitors

Sánchez-González

Bribián

2020

Sci Rep

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Determining the origin of different glial subtypes is crucial to understand glial heterogeneity, and to enhance our knowledge of glial and progenitor cell behavior in embryos and adults. NG2-glia are homogenously distributed in a grid-like manner in both, gray and white matter of the adult brain. While some NG2-glia in the CNS are responsible for the generation of mature oligodendrocytes (OPCs), most of them do not differentiate and they can proliferate outside of adult neurogenic niches. Thus, NG2-glia constitute a heterogeneous population containing different subpopulations with distinct functions. We hypothesized that their diversity emerges from specific progenitors during development, as occurs with other glial cell subtypes. To specifically target NG2-pallial progenitors and to define the NG2-glia lineage, as well as the NG2-progenitor potential, we designed two new StarTrack strategies using the NG2 promoter. These approaches label NG2 expressing progenitor cells, permitting the cell fates of these NG2 progenitors to be tracked in vivo. StarTrack labelled cells producing different neural phenotypes in different regions depending on the age targeted, and the strategy selected. This specific genetic targeting of neural progenitors in vivo has provided new data on the heterogeneous pool of NG2 progenitors at both embryonic and postnatal ages. NG2-glia are the main proliferative neural cells in the adult brain, representing about 5% of all the CNS cells 1-3. These cells are distributed homogeneously throughout the brain 4 and they are considered to be an independent population of glial cells, otherwise known as oligodendrocyte progenitor cells (OPCs) given that they can differentiate into oligodendrocytes during development, in the adult brain or after injury 5-7. One significant feature of NG2-glia is that they lack gap junction coupling yet they maintain a high input resistance, and they developing voltage-dependent sodium and potassium currents. These cells express ionotropic glutamate and GABA receptors and strikingly, they form direct synapses with neurons 8,9 , raising the possibility that they may modulate the activity of neurons and the operation of neural networks. During development, NG2-glia give rise to cells of the oligodendrocyte lineage and to a few astrocytes 10-12. In addition, these cells generate mature oligodendrocytes, although most of them do not differentiate into oligodendrocytes in the adult CNS 13,14 , rather they remain in a "progenitor" state. Indeed, the role of this undifferentiated population in the mature CNS remains largely unknown 15. What is known is that they increase in number following traumatic insults) and that they contribute to the formation of glial scars, suggesting they help limit neurodegeneration 1,16. Nevertheless, it is not clear whether these features are common to all NG2-glia cells or if there are different subpopulations that fulfil specific functions. Besides oligodendrocytes, NG2-glia have the potential to generate a variety of cell types like astrocytes a...

“…Due to the use of an ubiquitous promoter, the UbC-StarTrack methodology enables the progeny of embryonic and postnatal neural progenitors to be tracked in mice, irrespective of their fate [ 79 ]. Recently, to specifically track the descendants of NG2 progenitors, the promoter of either the transposase or transposon constructs was adapted accordingly [ 80 , 81 ]. Novel methods based on vector integration show high efficiency in terms of stable integration and the transmission of unique fingerprints to their descendants, which can be followed through several cell divisions and along different lineages through postnatal or adult stages.…”

Section: Introductionmentioning

confidence: 99%

Deciphering neural heterogeneity through cell lineage tracing

Figueres-Oñate

Sánchez-González

2020

Cell. Mol. Life Sci.

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Understanding how an adult brain reaches an appropriate size and cell composition from a pool of progenitors that proliferates and differentiates is a key question in Developmental Neurobiology. Not only the control of final size but also, the proper arrangement of cells of different embryonic origins is fundamental in this process. Each neural progenitor has to produce a precise number of sibling cells that establish clones, and all these clones will come together to form the functional adult nervous system. Lineage cell tracing is a complex and challenging process that aims to reconstruct the offspring that arise from a single progenitor cell. This tracing can be achieved through strategies based on genetically modified organisms, using either genetic tracers, transfected viral vectors or DNA constructs, and even single-cell sequencing. Combining different reporter proteins and the use of transgenic mice revolutionized clonal analysis more than a decade ago and now, the availability of novel genome editing tools and single-cell sequencing techniques has vastly improved the capacity of lineage tracing to decipher progenitor potential. This review brings together the strategies used to study cell lineages in the brain and the role they have played in our understanding of the functional clonal relationships among neural cells. In addition, future perspectives regarding the study of cell heterogeneity and the ontogeny of different cell lineages will also be addressed.