Although a considerable number of reports indicate an involvement of the Hox-A10 gene in the molecular control of hemopoiesis, the conclusions of such studies are quite controversial given that they support, in some cases, a role in the stimulation of stem cell self-renewal and myeloid progenitor expansion, whereas in others they implicate this transcription factor in the induction of monocyte-macrophage differentiation. To clarify this issue, we analyzed the biological effects and the transcriptome changes determined in human primary CD34+ hemopoietic progenitors by retroviral transduction of a full-length Hox-A10 cDNA. The results obtained clearly indicated that this homeogene is an inducer of monocyte differentiation, at least partly acting through the up-regulation of the MafB gene, recently identified as the master regulator of such a maturation pathway. By using a combined approach based on computational analysis, EMSA experiments, and luciferase assays, we were able to demonstrate the presence of a Hox-A10-binding site in the promoter region of the MafB gene, which suggested the likely molecular mechanism underlying the observed effect. Stimulation of the same cells with the vitamin D3 monocyte differentiation inducer resulted in a clear increase of Hox-A10 and MafB transcripts, indicating the existence of a precise transactivation cascade involving vitamin D3 receptor, Hox-A10, and MafB transcription factors. Altogether, these data allow one to conclude that the vitamin D3/Hox-A10 pathway supports MafB function during the induction of monocyte differentiation.

The vitamin D3/Hox-A10 pathway supports MafB function during the monocyte differentiation of human CD34+ hemopoietic progenitors / Gemelli, Claudia; Orlandi, Claudia; ZANOCCO MARANI, Tommaso; Martello, A; Vignudelli, Tatiana; Ferrari, Francesco; Montanari, Monica; Parenti, Sandra; Testa, Anna; Grande, Alexis; Ferrari, Sergio. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - STAMPA. - 181:(2008), pp. 5660-5672.

The vitamin D3/Hox-A10 pathway supports MafB function during the monocyte differentiation of human CD34+ hemopoietic progenitors.

GEMELLI, Claudia;ORLANDI, Claudia;ZANOCCO MARANI, Tommaso;VIGNUDELLI, Tatiana;FERRARI, Francesco;MONTANARI, Monica;PARENTI, Sandra;TESTA, Anna;GRANDE, Alexis;FERRARI, Sergio
2008-01-01

Abstract

Although a considerable number of reports indicate an involvement of the Hox-A10 gene in the molecular control of hemopoiesis, the conclusions of such studies are quite controversial given that they support, in some cases, a role in the stimulation of stem cell self-renewal and myeloid progenitor expansion, whereas in others they implicate this transcription factor in the induction of monocyte-macrophage differentiation. To clarify this issue, we analyzed the biological effects and the transcriptome changes determined in human primary CD34+ hemopoietic progenitors by retroviral transduction of a full-length Hox-A10 cDNA. The results obtained clearly indicated that this homeogene is an inducer of monocyte differentiation, at least partly acting through the up-regulation of the MafB gene, recently identified as the master regulator of such a maturation pathway. By using a combined approach based on computational analysis, EMSA experiments, and luciferase assays, we were able to demonstrate the presence of a Hox-A10-binding site in the promoter region of the MafB gene, which suggested the likely molecular mechanism underlying the observed effect. Stimulation of the same cells with the vitamin D3 monocyte differentiation inducer resulted in a clear increase of Hox-A10 and MafB transcripts, indicating the existence of a precise transactivation cascade involving vitamin D3 receptor, Hox-A10, and MafB transcription factors. Altogether, these data allow one to conclude that the vitamin D3/Hox-A10 pathway supports MafB function during the induction of monocyte differentiation.
181
5660
5672
The vitamin D3/Hox-A10 pathway supports MafB function during the monocyte differentiation of human CD34+ hemopoietic progenitors / Gemelli, Claudia; Orlandi, Claudia; ZANOCCO MARANI, Tommaso; Martello, A; Vignudelli, Tatiana; Ferrari, Francesco; Montanari, Monica; Parenti, Sandra; Testa, Anna; Grande, Alexis; Ferrari, Sergio. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - STAMPA. - 181:(2008), pp. 5660-5672.
Gemelli, Claudia; Orlandi, Claudia; ZANOCCO MARANI, Tommaso; Martello, A; Vignudelli, Tatiana; Ferrari, Francesco; Montanari, Monica; Parenti, Sandra; Testa, Anna; Grande, Alexis; Ferrari, Sergio
File in questo prodotto:
File Dimensione Formato  
Gemelli, Journal of Immunology 2008.pdf

non disponibili

Tipologia: Versione dell'autore revisionata e accettata per la pubblicazione
Dimensione 717.51 kB
Formato Adobe PDF
717.51 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento 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/11380/597379
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 23
social impact