bioRxivDevelopmental BiologyPreprint
Phosphorylation of 53BP1 by ATM enforce neurodevelopmental programs in cortical organoids
Bitna Lim, Mohamed Nadhir DjekideliD, Yurika MatsuiiD, Seung‐Hyun JungiD, Zuo‐Fei YuaniD, Xusheng WangiD, Xiaoyong YangiD, Abbas ShirinifardiD, Haitao PaniD, Fang WangiD, Shondra M. Pruett‐MilleriD, Kanisha Kavdia, Vishwajeeth PagalaiD, Yiping FaniD, Junmin PengiD, Beisi XuiD, Jamy C. PengiD
Abstract
53BP1 is a well-established DNA damage repair factor recently shown to regulate gene expression and critically influence tumor suppression and neural development. For gene regulation, how 53BP1 is regulated remains unclear. Here, we showed that 53BP1-serine 25 phosphorylation by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical organoids. 53BP1-serine 25 phosphorylation dynamics controls 53BP1 target genes for neuronal differentiation and function, cellular response to stress, and apoptosis. Beyond 53BP1, ATM is required for phosphorylation of factors in neuronal differentiation, cytoskeleton, p53 regulation, and ATM, BNDF, and WNT signaling pathways for cortical organoid differentiation. Overall, our data suggest that 53BP1 and ATM control key genetic programs required for human cortical development.
- organism: human
- research focus: cell type annotation
- research focus: differential expression
- research focus: gene regulatory network inference
- approach: experimental assay
- Citations
- 1
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