Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs during Differentiation and Regeneration

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• 作者：Eirini Trompouki¹ ;   ; ¹⁰ ; Teresa  ; V. Bowman¹ ;   ; ¹⁰ ; Lee  ; N. Lawton² ; Zi  ; Peng Fan² ;   ; ⁹ ; Dai-Chen Wu³ ;   ; ⁴ ; Anthony DiBiase¹ ; Corey  ; S. Martin¹ ; Jennifer  ; N. Cech¹ ; Anna  ; K. Sessa¹ ; Jocelyn  ; L. Leblanc¹ ; Pulin Li¹ ; Ellen  ; M. Durand¹ ; Christian Mosimann¹ ; Garrett  ; C. Heffner⁵ ;   ; ⁶ ;   ; ⁷ ;   ; ⁸ ; George  ; Q. Daley⁵ ;   ; ⁶ ;   ; ⁷ ;   ; ⁸ ; Robert  ; F. Paulson³ ;   ; ⁴ ; Richard  ; A. Young² ; Leonard  ; I. Zon¹ ;   ; ^{zon@enders.tch.harvard.edu}
• 刊名：Cell
• 出版年：2011
• 出版时间：28 October 2011
• 年：2011
• 卷：147
• 期：3
• 页码：577-589
• 全文大小：990 K

文摘

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Summary

BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to?hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBP¦Á in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBP¦Á, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity.