A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell Differentiation

Saxe, Jonathan P.; Wu, Hao; Kelly, Theresa K.; Phelps, Michael E.; Sun, Yi; Kornblum, Harley I.; Huang, Jing

doi:10.1016/j.chembiol.2007.07.016

Cited by 64 publications

(55 citation statements)

References 54 publications

(59 reference statements)

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“…As a result, several steroids that promoted hES cell differentiation were identified, and the antihypertensive drug pinacidil was shown to affect hES cell survival. Phenotypic screens can be advantageous because they can be carried out in cells by examining multiple markers and functional changes (for example, cell morphology and behavior) using automated high-content imaging technologies in a high-throughput manner [1,4,36,37] .…”

Section: High-throughput/content Screening (Primary Screen)mentioning

confidence: 99%

“…One study reported that phosphoserine (P-Ser) increased neurogenesis in hES cellderived neural progenitors [1] . It also confirmed that the effects of P-Ser are mediated by the group III metabotropic glutamate receptor 4 (mGluR4).…”

Section: A Series Of Secondary Assaysmentioning

confidence: 99%

“…Indirect approaches are based on a comparison of the genome-wide activity profile of the compound with databases of the activity profiles of other compounds with known targets or activity profiles following specific genetic changes. A variety of technologies and approaches have been explored for target identification after phenotypic screening [1,44,50] . Here, we would like to describe our recent work, which took advantage of chemical probing to identify signaling pathways involved in the differentiated state of ES cells (Figure 1).…”

Section: A Series Of Secondary Assaysmentioning

confidence: 99%

“…Mul- [13,16,17] . For example [1] , high-throughput identification of small molecules revealed that the orphan ligand phosphoserine (P-Ser) was an enhancer of neurogenesis. Saxe et al selectively modulated molecular, cellular, and systemlevel properties of the mammalian brain.…”

Section: A Series Of Secondary Assaysmentioning

confidence: 99%

“…An outstanding landmark in the past decade has been the development between stem cell biology and chemistry [1][2][3][4][5][6] . The combination of the two fields will likely provide an impetus for revealing intricate molecular interactions and functions under complex cellular differentiation, which offers systems for drug discovery and sources for potential cell therapy [7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

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Embryonic stem cell application in drug discovery

Lou¹,

Liang²

2011

Acta Pharmacol Sin

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Embryonic stem (ES) cells and their differentiated progeny offer tremendous potential for regenerative medicine, even in the field of drug discovery. There is an urgent need for clinically relevant assays that make use of ES cells because of their rich biological utility. Attention has been focused on small molecules that allow the precise manipulation of cells in vitro, which could allow researchers to obtain homogeneous cell types for cell-based therapies and discover drugs for stimulating the regeneration of endogenous cells. Such therapeutics can act on target cells or their niches in vivo to promote cell survival, proliferation, differentiation, and homing. In the present paper, we reviewed the use of ES cell models for high-throughput/content drug screening and toxicity assessment. In addition, we examined the role of stem cells in large pharmaceutical companies' R&D and discussed a novel subject, nicheology, in stem cellrelated research fields.

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Section: High-throughput/content Screening (Primary Screen)mentioning

confidence: 99%

Section: A Series Of Secondary Assaysmentioning

confidence: 99%

Section: A Series Of Secondary Assaysmentioning

confidence: 99%

Section: A Series Of Secondary Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Embryonic stem cell application in drug discovery

Lou¹,

Liang²

2011

Acta Pharmacol Sin

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Chemische Kontrolle des Schicksals und Entwicklungspotenzials von Stammzellen

et al. 2010

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Mögliche Anwendungen von Stammzellen in der Medizin reichen von der Modellierung von Krankheiten und der Wirkstoffsuche bis hin zu Zelltransplantation und regenerativen Therapien. Bevor diese Versprechen jedoch eingelöst werden können, müssen noch einige Hindernisse überwunden werden, unter anderem die Kontrolle der Stammzelldifferenzierung, die allogene Abstoßung und die eingeschränkte Zellverfügbarkeit. Dies erfordert ein vertieftes Verständnis der Mechanismen, die das Stammzellpotenzial kontrollieren, und die Entwicklung robuster Methoden, um das Schicksal von Stammzellen effizient zu steuern. In der letzten Zeit wurden eine Reihe niedermolekularer Verbindungen entdeckt, die in vitro und in vivo verwendet werden können, um Stammzellen zu expandieren, ihre Differenzierung zu dirigieren oder somatische Zellen in ein naiveres Stadium zu reprogrammieren. Diese Moleküle haben tiefe Einblicke in Signalwege und epigenetische Mechanismen ermöglicht, die die Stammzellbiologie regulieren, und sie beginnen bereits, zur Entwicklung effizienter Behandlungen für Gewebereparatur und –regeneration beizutragen.

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Chemical Control of Stem Cell Fate and Developmental Potential

et al. 2010

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Potential applications of stem cells in medicine range from their inclusion in disease modeling and drug discovery to cell transplantation and regenerative therapies. However, before this promise can be realized several obstacles must be overcome, including the control of stem cell differentiation, allogeneic rejection and limited cell availability. This will require an improved understanding of the mechanisms that govern stem cell potential and the development of robust methods to efficiently control their fate. Recently, a number of small molecules have been identified that can be used both in vitro and in vivo as tools to expand stem cells, direct their differentiation, or reprogram somatic cells to a more naive state. These molecules have provided a wealth of insights into the signaling and epigenetic mechanisms that regulate stem cell biology, and are already beginning to contribute to the development of effective treatments for tissue repair and regeneration.

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A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell Differentiation

Cited by 64 publications

References 54 publications

Embryonic stem cell application in drug discovery

Embryonic stem cell application in drug discovery

Chemische Kontrolle des Schicksals und Entwicklungspotenzials von Stammzellen

Chemical Control of Stem Cell Fate and Developmental Potential

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