Neural commitment of embryonic stem cells: molecules, pathways and potential for cell therapy

Suter, David M.; Krause, Karl‐Heinz

doi:10.1002/path.2380

Cited by 35 publications

(26 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our current knowledge of the mechanisms involved in neural cell formation is derived mostly from studying neurogenesis in the developing embryos of animal models (3,4). However, neurogenesis in animals is a complex process involving many different cell types that differentiate asynchronously.…”

mentioning

confidence: 99%

Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing

Habegger

Noisa

et al. 2010

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

176

165

View full text Add to dashboard Cite

To examine the fundamental mechanisms governing neural differentiation, we analyzed the transcriptome changes that occur during the differentiation of hESCs into the neural lineage. Undifferentiated hESCs as well as cells at three stages of early neural differentiation-N1 (early initiation), N2 (neural progenitor), and N3 (early glial-like)-were analyzed using a combination of single read, paired-end read, and long read RNA sequencing. The results revealed enormous complexity in gene transcription and splicing dynamics during neural cell differentiation. We found previously unannotated transcripts and spliced isoforms specific for each stage of differentiation. Interestingly, splicing isoform diversity is highest in undifferentiated hESCs and decreases upon differentiation, a phenomenon we call isoform specialization. During neural differentiation, we observed differential expression of many types of genes, including those involved in key signaling pathways, and a large number of extracellular receptors exhibit stage-specific regulation. These results provide a valuable resource for studying neural differentiation and reveal insights into the mechanisms underlying in vitro neural differentiation of hESCs, such as neural fate specification, neural progenitor cell identity maintenance, and the transition from a predominantly neuronal state into one with increased gliogenic potential.RNA-Seq | splicing isoforms | unannotated transcripts | neuron | glial N eural commitment and subsequent differentiation is a complex process. Although the complexity of RNAs expressed in neural tissues is very high (1, 2), a comprehensive analysis of the genes and RNA isoforms that are expressed during the different stages of neural cell differentiation is largely lacking. Such information is expected to be important for understanding mechanisms of neural cell differentiation and ultimately providing therapeutic solutions for neural degenerative diseases, such as Parkinson's and Alzheimer's disease.Our current knowledge of the mechanisms involved in neural cell formation is derived mostly from studying neurogenesis in the developing embryos of animal models (3, 4). However, neurogenesis in animals is a complex process involving many different cell types that differentiate asynchronously. This heterogeneity, along with the relatively small number of cells that can be readily obtained, makes the analysis of the temporal differentiation of individual cell types extremely difficult. One solution is to analyze hESCs during in vitro differentiation to different stages of neural development, which can be performed using a relatively large numbers of cells (5-9). Analysis of the transcriptome in these cells is expected to provide insights into the mechanisms and pathways involved in early cell fate specification, such as the acquisition of neurogenic potential and the transition to gliogenic potential, which may ultimately be extremely useful for pharmacologic screening and neurodegenerative disease therapies.Many high-throughput methods have...

show abstract

mentioning

confidence: 99%

Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing

Habegger

Noisa

et al. 2010

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

176

165

View full text Add to dashboard Cite

show abstract

“…Insulin promotes proliferation, transferrin promotes proliferation and survival of mature neurons, putrescine is involved in axonal regeneration, and selenium protects against excitotoxicity. B27 contains more than 20 components including vitamins, hormone growth factors, antioxidants, and fatty acids (Suter and Krause, 2008). Ectodermal factors are also used to restrict mesoderm differentiation using P53 pathway (Sasai et al, 2008).…”

Section: Hesc and Ipscs Differentiation Toward Neural Lineagementioning

confidence: 99%

Generation and Applications of Human Pluripotent Stem Cells Induced into Neural Lineages and Neural Tissues

Martinez¹,

Dubois‐Dauphin²,

Krause³

2012

Front. Physio.

View full text Add to dashboard Cite

Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern medicine, now the focus of many researchers and media outlets. The hype is well-earned because of the potential of stem cells to contribute to disease modeling, drug screening, and even therapeutic approaches. In this review, we focus first on neural differentiation of these cells. In a second part we compare the various cell types available and their advantages for in vitro modeling. Then we provide a “state-of-the-art” report about two major biomedical applications: (1) the drug and toxicity screening and (2) the neural tissue replacement. Finally, we made an overview about current biomedical research using differentiated hPSCs.

show abstract

“…Even more difficult is to obtain cell populations which are synchronized at a particular differentiation stage [1]. [2]). These approaches are cost-and labour intensive, and often result in the generation of heterogeneous cell populations.…”

Section: Embryonic Stem (Es) Cells Are Pluripotent Cells Derived Frommentioning

confidence: 99%

Phenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells

Suter¹,

Preynat‐Seauve²,

Tirefort³

et al. 2010

Journal of Cellular and Molecular Medicine

View full text Add to dashboard Cite

show abstract

Neural commitment of embryonic stem cells: molecules, pathways and potential for cell therapy

Cited by 35 publications

References 120 publications

Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing

Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing

Generation and Applications of Human Pluripotent Stem Cells Induced into Neural Lineages and Neural Tissues

Phenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells

Contact Info

Product

Resources

About