Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells
© 2014 John Wiley & Sons A/S..
Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron-committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2-based reporter cell line that expressed eGFP under the control of a neuron-specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2'-O-methyl substituted 2-deoxy-β-D-ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest-derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neurodegenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:86 |
|---|---|
| Enthalten in: |
Chemical biology & drug design - 86(2015), 2 vom: 01. Aug., Seite 129-43 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Raasch, Katharina [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adult human stem cell |
|---|
| Anmerkungen: |
Date Completed 02.06.2016 Date Revised 16.07.2015 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/cbdd.12488 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM243989245 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM243989245 | ||
| 003 | DE-627 | ||
| 005 | 20231224133722.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cbdd.12488 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0813.xml |
| 035 | |a (DE-627)NLM243989245 | ||
| 035 | |a (NLM)25444247 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Raasch, Katharina |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.06.2016 | ||
| 500 | |a Date Revised 16.07.2015 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2014 John Wiley & Sons A/S. | ||
| 520 | |a Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron-committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2-based reporter cell line that expressed eGFP under the control of a neuron-specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2'-O-methyl substituted 2-deoxy-β-D-ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest-derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neurodegenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a adult human stem cell | |
| 650 | 4 | |a cladribine | |
| 650 | 4 | |a human model neuron | |
| 650 | 4 | |a neuronal differentiation | |
| 650 | 4 | |a nucleoside analog | |
| 650 | 7 | |a Nucleosides |2 NLM | |
| 700 | 1 | |a Malecki, Edith |e verfasserin |4 aut | |
| 700 | 1 | |a Siemann, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Malayko M |e verfasserin |4 aut | |
| 700 | 1 | |a Heinisch, Jürgen J |e verfasserin |4 aut | |
| 700 | 1 | |a Müller, Janine |e verfasserin |4 aut | |
| 700 | 1 | |a Bakota, Lidia |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Rosemeyer, Helmut |e verfasserin |4 aut | |
| 700 | 1 | |a Brandt, Roland |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Chemical biology & drug design |d 2006 |g 86(2015), 2 vom: 01. Aug., Seite 129-43 |w (DE-627)NLM160848377 |x 1747-0285 |7 nnns |
| 773 | 1 | 8 | |g volume:86 |g year:2015 |g number:2 |g day:01 |g month:08 |g pages:129-43 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cbdd.12488 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 86 |j 2015 |e 2 |b 01 |c 08 |h 129-43 | ||