In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics

By M. Bonaguidi, Michael A. Wheeler, Jason S. Shapiro, R. Stadel, Gerald J. Sun, Guo-li Ming, Hongjun Song. 2011

839 citations recorded by the source corpus.

Summary Neurogenesis and gliogenesis continue in discrete regions of the adult mammalian brain. A fundamental question remains whether cell genesis occurs from distinct lineage-restricted progenitors or from self-renewing and multipotent neural stem cells in the adult brain. Here, we developed a genetic marking strategy for lineage-tracing of individual, quiescent, and nestin-expressing radial glia-like (RGL) precursors in the adult mouse dentate gyrus. Clonal analysis identified multiple modes of RGL activation, including asymmetric and symmetric self-renewal. Long-term lineage-tracing in vivo revealed a significant percentage of clones that contained RGL(s), neurons, and astrocytes, indicating capacity of individual RGLs for both self-renewal and multi-lineage differentiation. Furthermore, conditional Pten deletion in RGLs initially promotes their activation and symmetric self-renewal, but ultimately leads to terminal astrocytic differentiation and depletion in the adult hippocampus. Our study identifies RGLs as self-renewing and multipotent neural stem cells and provides novel insights into in vivo properties of adult neural stem cells.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Developmental Neuroscience

In Molecular Biology

Citations in the corpus

Human Hippocampal Neurogenesis Persists throughout Aging (2018, neutral): “, 2011), or a self-renewing multipotent neural stem cell pool that, after symmetric selfrenewal, undergoes terminal astrocytic differentiation (Bonaguidi et al., 2011).”
H3K4me3 breadth is linked to cell identity and transcriptional consistency (2014, background): “We chose adult neural progenitor cells (NPCs) because these cells give rise to all brain cell types and may be a source of cells for regenerative therapies (Bonaguidi et al., 2011; Doetsch et al., 1999; Lujan et al., 2012).”
Single-cell RNA-seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis (2015, methodology): “…a single low-dose tamoxifen injection into a Hopx-CreERT2 mouse line (Takeda et al., Cell S 2011) crossed with an mT/mGf/f reporter line for clonal lineage-tracing (Bonaguidi et al., 2011), almost all labeled precursors at 3 days post injection were nestin+GFAP+ qNSCs in the adult SGZ (Figure 3F).”
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, positive): “Clonal analysis of individual RGLs has revealed self-renewal andmultipotent capacities in this population (Bonaguidi et al., 2011).”
Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers (2017, background): “…cells in the rodent brain are capable of self-renewal (Suh et al., 2007) and that this ability persists throughout adulthood (Montaron et al., 1999; Hattiangady & Shetty, 2008; Bonaguidi et al., 2011), which may thus represent a tractable target for restoring age-related decreases in neurogenesis.”
Extracellular matrix: A dynamic microenvironment for stem cell niche (2014, background): “The intrinsic properties of NSCs present in the SGZ, such as self-renewal and multipotency, are still a matter of debate despite the fact that it was demonstrated that those cells can be isolated and cultured, generating self-renewing cells that can differentiate into neurons [202–205].”
Neuroinflammation and depression: A review (2020, background): “The birth of new neurons during adulthood undergoes a sequential process, starting with radial neural stem cells (rNSCs), which produce a copy of themselves together with neuroprogenitor (also known as type 2 cells) amplification (Bonaguidi et al., 2011; Encinas et al., 2011).”
Modification of hippocampal circuitry by adult neurogenesis (2012, background): “In vivo clonal analysis using a novel genetic labeling approach has demonstrated that radial glialike cells are capable of both self-renewal and multipotent differentiation into neurons and astrocytes (Bonaguidi et al., 2011).”
Leptin Receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow (2014, neutral): “Pten is cell-autonomously required for the maintenance of HSCs (Kalaitzidis et al., 2012; Lee et al., 2010; Magee et al., 2012; Yilmaz et al., 2006; Zhang et al., 2006) and neural stem cells (Bonaguidi et al., 2011).”
Adult hippocampal neurogenesis and its role in Alzheimer's disease (2011, background): “These new neurons originate from self-renewing and multipotent adult neural stem cells (NSCs) residing in the subgranular zone (SGZ) of DG [15].”
Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later (2015, background): “Single-cell genetic lineage-tracing has illustrated the existence of endogenous adult mammalian NSCs with hallmark stem cell properties (Bonaguidi et al., 2011).”