Human neurospheres derived from the fetal central nervous system are regionally and temporally specified but are not committed

Kim, Hyoung Tai; Kim, Il Sun; Lee, Il Shin; Lee, Jean Pyo; Snyder, Evan Y.; Park, Kook In

doi:10.1016/j.expneurol.2006.03.015

Cited by 110 publications

(116 citation statements)

References 74 publications

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“…Cotransfection experiment with BLBP-Cre and CAGGS-loxP-LacZ-loxP-YFP plasmids confirmed that RGs can differentiate into NeuN ϩ mature neurons. Moreover, we observed a small number of cells that were double labeled with specific RGs and neuronal markers, similar to previous reports (Skogh et al, 2001;Zecevic, 2004;Howard et al, 2006;Kim et al, 2006). These cells may represent multipotent progenitors, neurogenic RG cells, or intermediate progenitors (IPs) on their way to differentiate into neurons (Miyata et al, 2004;Noctor et al, 2004;Englund et al, 2005;Martinez-Cerdeno et al, 2006).…”

Section: Multipotent Progenitor Cellssupporting

confidence: 70%

Human Cortical Neurons Originate from Radial Glia and Neuron-Restricted Progenitors

Mo¹,

Moore²,

Filipovic³

et al. 2007

J. Neurosci.

103

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Understanding the molecular and physiological determinants of cortical neuronal progenitor cells is essential for understanding the development of the human brain in health and in disease. We used surface marker fucose N-acetyl lactosamine (LeX) (also known as CD15) to isolate progenitor cells from the cortical ventricular/subventricular zone of human fetal brain at the second trimester of gestation and to study their progeny in vitro.

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Section: Multipotent Progenitor Cellssupporting

confidence: 70%

Human Cortical Neurons Originate from Radial Glia and Neuron-Restricted Progenitors

Mo¹,

Moore²,

Filipovic³

et al. 2007

J. Neurosci.

103

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“…Indeed, the sources and methods of induction of NSCs are critical for differentiation and tumor formation [33,53]. Neurosphere cultures are heterogeneous and sensitive to variations in methodological procedures [12], whereas monolayer cell cultures give rise to more homogeneous population [13,14]. In this study, we detected no tumor Time course of functional recovery of hind limbs after SCI and DT administration.…”

Section: Discussionmentioning

confidence: 49%

“…hiPSCderived lt-NES (hiPS-lt-NES) cells exhibit consistent characteristics such as continuous expandability, stable neuronal and glial differentiation ability, and the capacity to generate functional mature neurons in monolayer culture. Whereas neurosphere cultures display heterogeneous character and are sensitive to variation in methodological procedures [12], monolayer cultures offer a more homogeneous and robust cell generation [13,14].…”

Section: Introductionmentioning

confidence: 99%

Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells

et al. 2012

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Because of their ability to self-renew, to differentiate into multiple lineages, and to migrate toward a damaged site, neural stem cells (NSCs), which can be derived from various sources such as fetal tissues and embryonic stem cells, are currently considered to be promising components of cell replacement strategies aimed at treating injuries of the central nervous system, including the spinal cord. Despite their efficiency in promoting functional recovery, these NSCs are not homogeneous and possess variable characteristics depending on their derivation protocols. The advent of induced pluripotent stem (iPS) cells has provided new prospects for regenerative medicine. We used a recently developed robust and stable protocol for the generation of long-term, self-renewing, neuroepithelial-like stem cells from human iPS cells (hiPS-lt-NES cells), which can provide a homogeneous and well-defined population of NSCs for standardized analysis. Here, we show that transplanted hiPS-lt-NES cells differentiate into neural lineages in the mouse model of spinal cord injury (SCI) and promote functional recovery of hind limb motor function. Furthermore, using two different neuronal tracers and ablation of the transplanted cells, we revealed that transplanted hiPS-lt-NES cell-derived neurons, together with the surviving endogenous neurons, contributed to restored motor function. Both types of neurons reconstructed the corticospinal tract by forming synaptic connections and integrating neuronal circuits. Our findings indicate that hiPS-lt-NES transplantation represents a promising avenue for effective cell-based treatment of SCI. Disclosure of potential conflicts of interest is found at the end of this article.

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“…Rodent and human embryo-derived neurospheres contain multipotent stem/ progenitor cells that can proliferate and differentiate into all neural lineages. Rodent neurospheres are excellent tools for, as an example, experimental studies in the areas of stem cell biology and brain repair (Reynolds and Weiss, 1996;Svendsen et al, 1999;Kim et al, 2006). Human neurospheres, conversely, could potentially be used in toxicity studies, screening novel drugs, and as an interesting potential source of cells for neural grafting in PD patients.…”

Section: Introductionmentioning

confidence: 99%

Effects on Differentiation of Embryonic Ventral Midbrain Progenitors by Lmx1a, Msx1, Ngn2, and Pitx3

Roybon¹,

Hjalt²,

Christophersen³

et al. 2008

J. Neurosci.

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Neurons derived from neural stem cells could potentially be used for cell therapy in neurodegenerative disorders, such as Parkinson's disease. To achieve controlled differentiation of neural stem cells, we expressed transcription factors involved in the development of midbrain dopaminergic neurons in rat and human neural progenitors. Using retroviral-mediated transgene delivery, we overexpressed Lmx1a (LIM homeobox transcription factor 1, alpha), Msx1 (msh homeobox homolog 1), Ngn2 (neurogenin 2), or Pitx3 (paired-like homeodomain transcription factor 3) in neurospheres derived from embryonic day 14.5 rat ventral mesencephalic progenitors. We also expressed either Lmx1a or Msx1 in the human embryonic midbrain-derived progenitor cell line NGC-407. Rat cells transduced with Ngn2 exited the cell cycle and expressed the neuronal marker microtubule-associated protein 2 and catecholamine-neuron protein vesicular monoamine transporter 2. Interestingly, Pitx3 downregulated the expression of SOX2 (SRY-box containing gene 2) and Nestin, altered cell morphology, but never induced neuronal or glial differentiation. Ngn2 exhibited a strong neuron-inducing effect. In contrast, few Lmx1a-transduced cells matured into neurons, and Msx1 overexpression promoted oligodendrogenesis rather than neuronal differentiation. Importantly, none of these four genes, alone or in combination, enhanced differentiation of rat neural stem cells into dopaminergic neurons. Notably, the overexpression of Lmx1a, but not Msx1, in human neural progenitors increased the yield of tyrosine hydroxylase-immunoreactive cells by threefold. Together, we demonstrate that induced overexpression of transcription factor genes has profound and specific effects on the differentiation of rat and human midbrain progenitors, although few dopamine neurons are generated.

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Human neurospheres derived from the fetal central nervous system are regionally and temporally specified but are not committed

Cited by 110 publications

References 74 publications

Human Cortical Neurons Originate from Radial Glia and Neuron-Restricted Progenitors

Human Cortical Neurons Originate from Radial Glia and Neuron-Restricted Progenitors

Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells

Effects on Differentiation of Embryonic Ventral Midbrain Progenitors by Lmx1a, Msx1, Ngn2, and Pitx3

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