Committed Neuronal Precursors Confer Astrocytic Potential on Residual Neural Precursor Cells

Namihira, Masakazu; Kohyama, Jun; Semi, Katsunori; Sanosaka, Tsukasa; Deneen, Benjamin; Taga, Tetsuya; Nakashima, Kinichi

doi:10.1016/j.devcel.2008.12.014

Cited by 320 publications

(348 citation statements)

References 54 publications

Supporting

Mentioning

334

Contrasting

Unclassified

Order By: Relevance

“…NPCs were cultured in suspension as neurospheres in medium containing epidermal growth factor (EGF) and leukemia inhibitory factor (LIF) for 4-6 wk. In the absence of fibroblast growth factor 2 (FGF2), coapplication of EGF and LIF in prolonged culture promoted astroglial specification of NPCs (13,14) and efficiently selected for neurospheres with a high content of astroglial progenitors. After this enrichment phase, neurospheres were expanded in EGF-and FGF2-containing medium before enzymatic dissociation to single cells.…”

Section: Resultsmentioning

confidence: 99%

Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy

Serio

Bilican

Barmada

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

308

331

View full text Add to dashboard Cite

Glial proliferation and activation are associated with disease progression in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia. In this study, we describe a unique platform to address the question of cell autonomy in transactive response DNAbinding protein (TDP-43) proteinopathies. We generated functional astroglia from human induced pluripotent stem cells carrying an ALScausing TDP-43 mutation and show that mutant astrocytes exhibit increased levels of TDP-43, subcellular mislocalization of TDP-43, and decreased cell survival. We then performed coculture experiments to evaluate the effects of M337V astrocytes on the survival of wild-type and M337V TDP-43 motor neurons, showing that mutant TDP-43 astrocytes do not adversely affect survival of cocultured neurons. These observations reveal a significant and previously unrecognized glial cell-autonomous pathological phenotype associated with a pathogenic mutation in TDP-43 and show that TDP-43 proteinopathies do not display an astrocyte non-cell-autonomous component in cell culture, as previously described for SOD1 ALS. This study highlights the utility of induced pluripotent stem cell-based in vitro disease models to investigate mechanisms of disease in ALS and other TDP-43 proteinopathies.glia | motor neuron disease | disease modeling T ransactive response DNA-binding protein (TDP-43) is the major component of ubiquitinated cytoplasmic and nuclear inclusions in neurons and astroglia in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP) (1-3). These pathological hallmarks provide a unifying description of a range of conditions defined as TDP-43 proteinopathies (4). At present, >30 mutations in the TDP-43 gene (TARDBP) have been linked to familial ALS (fALS) (5), strongly suggesting a causative role for TDP-43 in the pathogenesis of ALS.Accumulating evidence from experimental systems implicating non-cell-autonomous mechanisms in ALS has highlighted the importance of the glial cellular environment to motor neuron (MN) degeneration (1,3,(6)(7)(8)(9). In vivo rodent models of ALS with lineage-specific SOD1 expression have particularly influenced our understanding of the nonneuronal contribution to disease progression. Glial expression of mutant SOD1 cannot initiate MN disease on its own, but is necessary for disease progression (6, 7). Furthermore, astrogliosis precedes MN degeneration in some animal models and is a dominant feature of all human ALS pathology (4, 6, 10). Collectively, these observations highlight the need to better understand the nature of astroglial pathology in ALS. Combining developmental neurobiological principles of cell fate determination with human induced pluripotent stem cell (iPSC) lines derived from patients carrying ALS disease-causing mutations may provide important insights into astroglia pathology.We recently generated human MNs from iPSC lines derived from a fALS patient and demonstrated that the M337V TDP-43 mutation confers cell-autonomous toxicity to MNs (11). More...

show abstract

Section: Resultsmentioning

confidence: 99%

Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy

Serio

Bilican

Barmada

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

308

331

View full text Add to dashboard Cite

show abstract

“…In fact, two Drosophila Foxg1 orthologs, Sloppy paired-1 and -2 (Slp1 and Slp2), promote neuronogenesis at expenses of gliogenesis [59] and Foxg1 rescues the Slp1&2 null phenotype [60]. Such aberrant behavior of Foxg1-GOF NSCs might originate from unbalanced expression of Hes1, a key promoter of NSC self-renewal [61] and key gliogenesis promoters Coup-tf1, Nf1a, and Olig2 [62][63][64] (Supporting Information Fig. S11).…”

Section: Foxg1 Inhibits Gliogenesis and Potentiates Neuronogenesis Smentioning

confidence: 99%

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

et al. 2010

View full text Add to dashboard Cite

Neural stem cells (NSCs) give rise to all cell types forming the cortex: neurons, astrocytes, and oligodendrocytes. The transition from the former to the latter ones takes place via lineage-restricted progenitors in a highly regulated way. This process is mastered by large sets of genes, among which some implicated in central nervous system pattern formation. The aim of this study was to disentangle the kinetic and histogenetic roles exerted by two of these genes, Emx2 and Foxg1, in cortico-cerebral precursors. For this purpose, we set up a new integrated in vitro assay design. Embryonic cortical progenitors were transduced with lentiviral vectors driving overexpression of Emx2 and Foxg1 in NSCs and neuronal progenitors. Cells belonging to different neuronogenic and gliogenic compartments were labeled by spectrally distinguishable fluoroproteins driven by cell type-specific promoters and by cell type-specific antibodies and were scored via multiplex cytofluorometry and immunocytofluorescence. A detailed picture of Emx2 and Foxg1 activities in cortico-cerebral histogenesis resulted from this study. Unexpectedly, we found that both genes inhibit gliogenesis and promote neuronogenesis, through distinct mechanisms, and Foxg1 also dramatically stimulates neurite outgrowth. Remarkably, such activities, alone or combined, may be exploited to ameliorate the neuronal output obtainable from neural cultures, for purposes of cell-based brain repair. STEM CELLS

show abstract

“…L'activation de Notch résulte en l'induction du facteur de transcription NF1A (nuclear factor 1A), qui permet la déméthylation du promoteur du gène codant le marqueur astrocytaire GFAP (glial fibrillary acidic protein). Le promoteur ainsi déméthylé est activé dès que les cellules reçoivent un signal activateur dérivé de la voie Jak/Stat (Janus kinase/signal transducer and activator of transcription) [21]. Plusieurs mécanismes permettent d'éviter une production excessive d'astrocytes comme la répression de Hes1 par NF1A ou la dégradation du récepteur Notch1 par l'ubiquitine ligase Fbxw7 en fonction du stade de développement des CSN [22].…”

Section: Rôle De Notch Dans La Différenciation Neuronale Et L'équilibunclassified

Cellules souches neurales et signalisation Notch

Traiffort

Ferent

2015

Med Sci (Paris)

View full text Add to dashboard Cite

> Les cellules souches neurales (CSN) sont essentielles au développement du système nerveux central et à sa réparation. Parmi les mécanismes contrôlant ces cellules, la signalisation Notch joue un rôle majeur. Chez l'embryon, elle permet le maintien des CSN pendant les différentes phases de développement du système nerveux central qui débute par la production des neurones, ou neurogenèse, et se poursuit par la gliogenèse conduisant aux astrocytes et oligodendrocytes. Au cours de la période post-natale et adulte, la signalisation Notch reste présente dans les principales aires de neurogenèse adulte, la zone sous-ventriculaire des ventricules latéraux et la zone sous-granulaire de l'hippocampe, où elle maintient la quiescence des CSN adultes, contribue au caractère hétérogène de ces cellules et exerce des effets pléiotropes au cours de la régénération du tissu neural lésé. < elle participe à la résistance des cellules cancéreuses aux agents cytotoxiques. Dans cette revue, nous nous focaliserons sur l'implication de la signalisation Notch dans la régulation des cellules souches neurales (CSN) durant le développement et chez l'adulte, et considérerons son activité dans un contexte physiologique ou pathologique. Au cours du développement embryonnaire, les CSN sont capables de s'auto-renouveler et de générer les lignages conduisant à la formation des neurones, astrocytes et oligodendrocytes. Il y a quelques décennies, la persistance de CSN dans des régions bien définies du système nerveux central (SNC) adulte fut démontrée et suscita beaucoup d'intérêt car elle offrait des perspectives théra-peutiques prometteuses pour lutter contre les processus dégéné-ratifs du cerveau et de la moelle épinière. La connaissance approfondie des mécanismes moléculaires qui contrôlent la genèse, le maintien et la détermination des CSN est par conséquent d'une importance majeure. Parmi ces mécanismes, on trouve les signalisations Bmp (bone morphogenetic proteins), Wnt, Shh (sonic hedgehog) et Notch [46] (➜). La signalisation Bmp possède une activité mitogène sur les CSN embryonnaires, mais favorise la quiescence des CSN adultes. La signalisation Wnt, de son côté, induit une activité proliférative sur ces deux types cellulaires. Le morphogène Shh est impliqué dans la mise en place des différents domaines où se localisent les cellules progénitrices dans le système nerveux en développement, puis dans l'établissement et le maintien de ceux où persistent les CSN post-natales et adultes. Comme illustré dans cette revue, la voie Notch orchestre dans le temps la production des neurones et des cellules gliales, et maintient l'état indifférencié des CSN embryonnaires et adultes. Conservée durant l'évolution des espèces, la signalisation Notch est essentielle au cours du dévelop-pement des invertébrés et des vertébrés. Sa capacité à contrôler les interactions cellule-cellule ainsi que la prolifération, la différenciation ou l'apoptose de divers types cellulaires lui confère un rôle majeur dans la genèse de nombreuses cellules notamment nerveuses, m...

show abstract

Committed Neuronal Precursors Confer Astrocytic Potential on Residual Neural Precursor Cells

Cited by 320 publications

References 54 publications

Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy

Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

Cellules souches neurales et signalisation Notch

Contact Info

Product

Resources

About