Abstract:
:Atypical teratoid rhabdoid tumors (ATRTs) are challenging pediatric brain cancers that are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SMARCB1 loss and the process of neural development, we introduced an inducible SMARCB1 loss-of-function system into human induced pluripotent stem cells (iPSCs) that were subjected to either directed neuronal differentiation or differentiation into cerebral organoids. Using this system, we identified substantial differences in the downstream effects of SMARCB1 loss depending on differentiation state and identified an interaction between SMARCB1 loss and neural differentiation pressure that causes a resistance to terminal differentiation and a defect in maintenance of a normal cell state. Our results provide insight into how SMARCB1 loss might interact with neural development in the process of ATRT tumorigenesis.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Parisian AD,Koga T,Miki S,Johann PD,Kool M,Crawford JR,Furnari FBdoi
10.1101/gad.339978.120subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1316-1329issue
19-20eissn
0890-9369issn
1549-5477pii
gad.339978.120journal_volume
34pub_type
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