Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here, we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival, indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem-cell commitment during neurogenesis. © 2013 European Molecular Biology Organization.

Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment / Aprea, Julieta; Prenninger, Silvia; Dori, Martina; Ghosh, Tanay; Monasor, Laura Sebastian; Wessendorf, Elke; Zocher, Sara; Massalini, Simone; Alexopoulou, Dimitra; Lesche, Mathias; Dahl, Andreas; Groszer, Matthias; Hiller, Michael; Calegari, Federico. - In: EMBO JOURNAL. - ISSN 0261-4189. - 32:24(2013), pp. 3145-3160. [10.1038/emboj.2013.245]

Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment

Dori, Martina;
2013

Abstract

Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here, we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival, indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem-cell commitment during neurogenesis. © 2013 European Molecular Biology Organization.
2013
32
24
3145
3160
Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment / Aprea, Julieta; Prenninger, Silvia; Dori, Martina; Ghosh, Tanay; Monasor, Laura Sebastian; Wessendorf, Elke; Zocher, Sara; Massalini, Simone; Alexopoulou, Dimitra; Lesche, Mathias; Dahl, Andreas; Groszer, Matthias; Hiller, Michael; Calegari, Federico. - In: EMBO JOURNAL. - ISSN 0261-4189. - 32:24(2013), pp. 3145-3160. [10.1038/emboj.2013.245]
Aprea, Julieta; Prenninger, Silvia; Dori, Martina; Ghosh, Tanay; Monasor, Laura Sebastian; Wessendorf, Elke; Zocher, Sara; Massalini, Simone; Alexopou...espandi
File in questo prodotto:
File Dimensione Formato  
Prenninger.pdf

Accesso riservato

Descrizione: Articolo principale
Tipologia: Versione originale dell'autore proposta per la pubblicazione
Dimensione 315.33 kB
Formato Adobe PDF
315.33 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1158014
Citazioni
  • ???jsp.display-item.citation.pmc??? 99
  • Scopus 180
  • ???jsp.display-item.citation.isi??? 177
social impact