Dysregulation of the Transforming Growth Factor β Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia
Fig 7
Molecular model of dysregulation of TGFβ signaling in DBA iPSCs.
Ribosomal haploinsufficiency may lead to an increasing expression of TGFβ downstream targets through non-canonical JNK signaling. We also identified an increased proteolytic turnover of SMAD4 in the DBA iPSCs. The activation of TGFβ signaling contributes to the reduced differentiation of erythroid cells, and the decrease of SMAD4 could be the major factor permitting DBA iPSCs to proliferate.