Embryonic Origin of Postnatal Neural Stem Cells

Fuentealba, Luis C.; Rompani, Santiago B.; Parraguez, Jose I.; Obernier, Kirsten; Romero, Rafael Ramírez; Cepko, Constance L.; Alvarez-Buylla, Arturo

doi:10.1016/j.cell.2015.05.041

Cited by 406 publications

(449 citation statements)

References 54 publications

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“…The prevailing model suggested that radial glia transform, after they produce neurons and glia in the embryo, into B1 cells (Kriegstein and Alvarez-Buylla 2009). This simple view is challenged by a recent lineage tracing study that investigates the pedigree of adult B1 cells (Fuentealba et al 2015). The new results show that postnatal B1 cells are indeed derived from embryonic NSCs that produce also neurons and glia for other forebrain regions (including cortex, striatum, and septum).…”

Section: The Search For Markers Of Type B1 Cellsmentioning

confidence: 71%

The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis

Lim

Alvarez-Buylla

2016

Cold Spring Harb Perspect Biol

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A large population of neural stem/precursor cells (NSCs) persists in the ventricular-subventricular zone (V-SVZ) located in the walls of the lateral brain ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long distance into the olfactory bulb (OB) where they differentiate into local circuit interneurons. Here, we review a broad range of discoveries that have emerged from studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of neuronal migration, and molecular regulators of precursor cell proliferation and migration. It has also become evident that V-SVZ NSCs are regionally heterogeneous, with NSCs located in different regions of the ventricle wall generating distinct OB interneuron subtypes. Insights into the developmental origins and molecular mechanisms that underlie the regional specification of V-SVZ NSCs have also begun to emerge. Other recent studies have revealed new cellintrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ. Finally, we discuss intriguing differences between the rodent V-SVZ and the corresponding human brain region. The rapidly expanding cellular and molecular knowledge of V-SVZ NSC biology provides key insights into postnatal neural development, the origin of brain tumors, and may inform the development regenerative therapies from cultured and endogenous human neural precursors. N ew neurons continue to be added throughout life to the olfactory bulb (OB) in the brain of many mammals. In rodents, the adult germinal region for OB neurogenesis is located along the walls of the brain lateral ventricles. Recent results regarding the spatial arrangement and cellular morphology of the primary neural precursors-or, neural stem cells (NSCs)-indicate that this region has characteristics similar to both the embryonic ventricular zone (VZ) and subventricular zone (SVZ). Given this new understanding, we now refer to this region as the ventricular-subventricular zone (V-SVZ).Neuroblasts born from NSCs in the mouse V-SVZ migrate rostrally into the OB where they then disperse radially and differentiate into functional interneurons (Fig. 1). Several distinct interneuron subtypes are generated by the V-SVZ, and estimates indicate that thousands of new OB neurons are generated every day in the young adult rodent brain.

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Section: The Search For Markers Of Type B1 Cellsmentioning

confidence: 71%

The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis

Lim

Alvarez-Buylla

2016

Cold Spring Harb Perspect Biol

Self Cite

484

428

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“…For other datasets, differing in the number or identity of the sampled tissues, there may be less of an a priori expectation for the shape of the ontogenetic phylogeny. While there is a general understanding of the major divisions of tissues during development, the embryonic origins and lineage of somatic germ cell populations are not straightforward and still being established (e.g., Romagnani et al, 2015;Fuentealba et al, 2015;Boisset and Robin, 2012). The current model could easily be extended to ontogenetic phylogenies for families with two or more offspring.…”

Section: Discussionmentioning

confidence: 99%

A Population Phylogenetic View of Mitochondrial Heteroplasmy

et al. 2018

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The mitochondrion has recently emerged as an active player in a myriad of cellular processes. Additionally, it was recently shown that more than 200 diseases are known to be linked to variants in mitochondrial DNA or in nuclear genes interacting with mitochondria. This has reinvigorated interest in its biology and population genetics. Mitochondrial heteroplasmy, or genotypic variation of mitochondria within an individual, is now understood to be common in humans and important in human health. However, it is still not possible to make quantitative predictions about the inheritance of heteroplasmy and its proliferation within the body, partly due to the lack of an appropriate model. Here, we present a population-genetic framework for modeling mitochondrial heteroplasmy as a process that occurs on an ontogenetic phylogeny, with genetic drift and mutation changing heteroplasmy frequencies during the various developmental processes represented in the phylogeny. Using this framework, we develop a Bayesian inference method for inferring rates of mitochondrial genetic drift and mutation at different stages of human life. Applying the method to previously published heteroplasmy frequency data, we demonstrate a severe effective germline bottleneck comprised of the cumulative genetic drift occurring between the divergence of germline and somatic cells in the mother and the separation of germ layers in the offspring. Additionally, we find that the two somatic tissues we analyze here undergo tissue-specific bottlenecks during embryogenesis, less severe than the effective germline bottleneck, and that these somatic tissues experience little additional genetic drift during adulthood. We conclude with a discussion of possible extensions of the ontogenetic phylogeny framework and its possible applications to other ontogenetic processes in addition to mitochondrial heteroplasmy.

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“…spiral ganglion, vestibular epithelium or OC. Potency of neural stem cells has been difficult to determine without adequate markers to use for tracing the lineage of progenitor cells and for the differentiated progeny, and, as a result, similar questions have remained unresolved in several neural and non-neural stem cell compartments (Fuentealba et al, 2015). Here, by using gene expression analysis and physiological properties, as well as lineage tracing of putative progenitors in the spiral ganglion, OC and vestibular epithelia, we could identify nine distinct cell types, which allowed us to determine whether the progenitor cells were uni-, multi-or pluripotent.…”

Section: Introductionmentioning

confidence: 99%

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

McLean

Eatock

et al. 2016

Development

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Disorders of hearing and balance are most commonly associated with damage to cochlear and vestibular hair cells or neurons. Although these cells are not capable of spontaneous regeneration, progenitor cells in the hearing and balance organs of the neonatal mammalian inner ear have the capacity to generate new hair cells after damage. To investigate whether these cells are restricted in their differentiation capacity, we assessed the phenotypes of differentiated progenitor cells isolated from three compartments of the mouse inner ear -the vestibular and cochlear sensory epithelia and the spiral ganglion -by measuring electrophysiological properties and gene expression. Lgr5 + progenitor cells from the sensory epithelia gave rise to hair cell-like cells, but not neurons or glial cells. Newly created hair cell-like cells had hair bundle proteins, synaptic proteins and membrane proteins characteristic of the compartment of origin. PLP1 + glial cells from the spiral ganglion were identified as neural progenitors, which gave rise to neurons, astrocytes and oligodendrocytes, but not hair cells. Thus, distinct progenitor populations from the neonatal inner ear differentiate to cell types associated with their organ of origin.

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Embryonic Origin of Postnatal Neural Stem Cells

Cited by 406 publications

References 54 publications

The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis

The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis

A Population Phylogenetic View of Mitochondrial Heteroplasmy

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

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