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Steinbeck JA Koch P Derouiche A Brüstle O 《Cellular and molecular life sciences : CMLS》2012,69(3):461-470
While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system
repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved.
We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES
cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific
markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro,
lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a
composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted
projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal
grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons
of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and
via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles
was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural
correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent
stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain. 相似文献
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Getting there and being there in the cerebral cortex 总被引:1,自引:0,他引:1
M. Götz 《Cellular and molecular life sciences : CMLS》1995,51(4):301-316
The mammalian neocortex is composed of functional areas that are specified to process particular aspects of information. How is this specification achieved during development? Since cells migrate to their final positions in the developing nervous system, a central issue is the relation between cellular migration and positional information. This review combines evidence for early positional specification in the developing cortex with evidence for cellular dispersion during migration. A model is suggested whereby stable cues provide positional information and minorities of ‘displaced’ cells are respecified accordingly. Comparison with other parts of the CNS reveals that cellular dispersal is ubiquitous and has to be included in any mechanism relaying positional specification. Ontogenetic and phylogenetic considerations suggest that radial glial cells might provide the positional information in the developing nervous system. 相似文献
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Michele Bertacchi Luca Pandolfini Elisa Murenu Alessandro Viegi Simona Capsoni Alessandro Cellerino Andrea Messina Simona Casarosa Federico Cremisi 《Cellular and molecular life sciences : CMLS》2013,70(6):1095-1111
We investigated the effects of bone morphogenetic proteins (BMPs) in determining the positional identity of neurons generated in vitro from mouse embryonic stem cells (ESCs), an aspect that has been neglected thus far. Classical embryological studies in lower vertebrates indicate that BMPs inhibit the default fate of pluripotent embryonic cells, which is both neural and anterior. Moreover, mammalian ESCs generate neurons more efficiently when cultured in a minimal medium containing BMP inhibitors. In this paper, we show that mouse ESCs produce, secrete, and respond to BMPs during in vitro neural differentiation. After neuralization in a minimal medium, differentiated ESCs show a gene expression profile consistent with a midbrain identity, as evaluated by the analysis of a number of markers of anterior–posterior and dorsoventral identity. We found that BMPs endogenously produced during neural differentiation mainly act by inhibiting the expression of a telencephalic gene profile, which was revealed by the treatment with Noggin or with other BMP inhibitors. To better characterize the effect of BMPs on positional fate, we compared the global gene expression profiles of differentiated ESCs with those of embryonic forebrain, midbrain, and hindbrain. Both Noggin and retinoic acid (RA) support neuronal differentiation of ESCs, but they show different effects on their positional identity: whereas RA supports the typical gene expression profile of hindbrain neurons, Noggin induces a profile characteristic of dorsal telencephalic neurons. Our findings show that endogenously produced BMPs affect the positional identity of the neurons that ESCs spontaneously generate when differentiating in vitro in a minimal medium. The data also support the existence of an intrinsic program of neuronal differentiation with dorsal telencephalic identity. Our method of ESC neuralization allows for fast differentiation of neural cells via the same signals found during in vivo embryonic development and for the acquisition of cortical identity by the inhibition of BMP alone. 相似文献
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Koninckx R Daniëls A Windmolders S Carlotti F Mees U Steels P Rummens JL Hendrikx M Hensen K 《Cellular and molecular life sciences : CMLS》2011,68(12):2141-2156
In the past, clinical trials transplanting bone marrow–derived mononuclear cells reported a limited improvement in cardiac
function. Therefore, the search for stem cells leading to more successful stem cell therapies continues. Good candidates are
the so-called cardiac stem cells (CSCs). To date, there is no clear evidence to show if these cells are intrinsic stem cells
from the heart or mobilized cells from bone marrow. In this study we performed a comparative study between human mesenchymal
stem cells (hMSCs), purified c-kit+ CSCs, and cardiosphere-derived cells (CDCs). Our results showed that hMSCs can be discriminated from CSCs by their differentiation
capacity towards adipocytes and osteocytes and the expression of CD140b. On the other hand, cardiac progenitors display a
greater cardiomyogenic differentiation capacity. Despite a different isolation protocol, no distinction could be made between
c-kit+ CSCs and CDCs, indicating that they probably derive from the same precursor or even are the same cells. 相似文献
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T. Mueller J. Luetzkendorf K. Nerger H.-J. Schmoll L. P. Mueller 《Cellular and molecular life sciences : CMLS》2009,66(3):495-503
OCT4 is considered a main regulator of embryonic stem cell pluripotency and self renewal capacity. It was shown that relevant
OCT4 expression only occurs in cells of embryonic pluripotent nature. However, several recent publications claimed to have
demonstrated OCT4 expression in human somatic tumor cells, human adult stem or progenitor cells and differentiated cells.We
analysed 42 human tumor cell lines from 13 entities and human bone marrowderived mesenchymal stem cells (MSC). To validate
OCT4 expression we used germ cell tumor (GCT) cell lines, derived xenografts and GCT samples. Analysis by RT-PCR, western
blotting, immunocytochemistry and immunohistochemistry was performed. With exception of typical embryonal carcinoma cells,
we did not observe reliable OCT4 expression in somatic tumor cell lines and MSC. We suggest that a high level of expression
of the OCT4 protein together with its nuclear localization still remains a reliable and definitive feature of cells with embryonic
pluripotent nature.
Received 30 September 2008; received after revision 05 November 2008; accepted 10 November 2008 相似文献
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Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences 总被引:1,自引:1,他引:0
Wislet-Gendebien S Laudet E Neirinckx V Alix P Leprince P Glejzer A Poulet C Hennuy B Sommer L Shakhova O Rogister B 《Cellular and molecular life sciences : CMLS》2012,69(15):2593-2608
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Ohira K 《Cellular and molecular life sciences : CMLS》2011,68(10):1645-1656
It has been accepted that new neurons are added to the olfactory bulb and the hippocampal dentate gyrus throughout life in
the healthy adult mammalian brain. Recent studies have clarified that brain insult raises the proliferation of neural stem
cells/neural progenitor cells existing in the subventricular zone and the subgranular zone, which become sources of new neurons
for the olfactory bulb and the dentate gyrus, respectively. Interestingly, convincing data has shown that brain insult invokes
neurogenesis in various brain regions, such as the hippocampal cornu ammonis region, striatum, and cortex. These reports suggest
that neural stem cells/neural progenitor cells, which can be activated by brain injury, might be broadly located in the adult
brain or that new neurons may migrate widely from the neurogenic regions. This review focuses on brain insult-induced neurogenesis
in the mammalian forebrain, especially in the neocortex. 相似文献
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