Modeling the function of BAX and BAK in early human brain development using iPSC-derived systems.
Modeling the function of BAX and BAK in early human brain development using iPSC-derived systems.
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DOI：
10.1038/s41419-020-03002-x
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发表时间：
2020-09-25
影响因子：
9
通讯作者：
Gama V
中科院分区：
文献类型：
--
作者：
Joshi P;Bodnya C;Rasmussen ML;Romero-Morales AI;Bright A;Gama V
Intrinsic apoptosis relies on the ability of the BCL-2 family to induce the formation of pores on the outer mitochondrial membrane. Previous studies have shown that both BAX and BAK are essential during murine embryogenesis, and reports in human cancer cell lines identified non-canonical roles for BAX and BAK in mitochondrial fission during apoptosis. BAX and BAK function in human brain development remains elusive due to the lack of appropriate model systems. Here, we generated BAX/BAK double knockout human-induced pluripotent stem cells (hiPSCs), hiPSC-derived neural progenitor cells (hNPCs), neural rosettes, and cerebral organoids to uncover the effects of BAX and BAK deletion in an in vitro model of early human brain development. We found that BAX and BAK-deficient cells have abnormal mitochondrial morphology and give rise to aberrant cortical structures. We suggest crucial functions for BAX and BAK during human development, including maintenance of homeostatic mitochondrial morphology, which is crucial for proper development of progenitors and neurons of the cortex. Human pluripotent stem cell-derived systems can be useful platforms to reveal novel functions of the apoptotic machinery in neural development.
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影响因子：
16
作者：
Dumitru, Raluca;Gama, Vivian;Fagan, B. Matthew;Bower, Jacquelyn J.;Swahari, Vijay;Pevny, Larysa H.;Deshmukh, Mohanish
通讯作者：
Deshmukh, Mohanish
DOI：
10.1073/pnas.0703976104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Brooks, Craig;Wei, Qingqing;Dong, Zheng
通讯作者：
Dong, Zheng
影响因子：
1.2
作者：
Fedorova, Veronika;Vanova, Tereza;Bohaciakova, Dasa
通讯作者：
Bohaciakova, Dasa
影响因子：
4
作者：
Einsele-Scholz, Stephanie;Malmsheimer, Silke;Essmann, Frank
通讯作者：
Essmann, Frank
影响因子：
16
作者：
Hoppins S;Edlich F;Cleland MM;Banerjee S;McCaffery JM;Youle RJ;Nunnari J
通讯作者：
Nunnari J