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Co-IP protein identification of WT/MT IVNS1ABP in isogenic iPSCs derived NPCs

ABSTRACT: We identified a new disease characterized by severe neurological deficits in addition to progeria symptoms. It is caused by IVNSABP gene mutation. The association between IVNS1ABP and aging has never been reported before. By generating isogenic iPSCs from the patients’ fibroblasts and differentiating the iPSCs into neural progenitor cells (NPCs),we performed a pull-down assay with an IVNS1ABP antibody, followed by mass spectrometry to identify the potential protein interactors of both wild type (Ctrl) and MT IVNS1ABP using NPCs from the isogenic pairs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Progeria

SUBMITTER: Fang YUAN

LAB HEAD: Su-Chun Zhang

PROVIDER: PXD053645 | Pride | 2026-01-23

REPOSITORIES: Pride

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			Action	DRS
	01Apr21_Duke_Control_R1.raw	Raw
	01Apr21_Duke_Control_R2.raw	Raw
	01Apr21_Duke_Control_R3.raw	Raw
	01Apr21_Duke_IGG_R1.raw	Raw
	01Apr21_Duke_IGG_R2.raw	Raw

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Project description:We identified a new disease characterized by severe neurological deficits in addition to progeria symptoms. It is caused by IVNSABP gene mutation. The association between IVNS1ABP and aging has never been reported before. By generating isogenic iPSCs from the patients’ fibroblasts and differentiating the iPSCs into neural progenitor cells (NPCs), we found that mutant IVNS1ABP fibroblasts, iPSCs, and NPCs exhibited disrupted cytokinesis, DNA damage, and cellular senescence. Transcription analysis of isogenic iPSCs and iPSCs derived neural progenitors (NPCs) also showed impaired cytokinesis and senescence alteration. Correspondingly, cerebral organoids displayed premature differentiation of NPCs to neurons. Molecular profiling as well as biochemical and cellular analysis revealed altered binding of mutant IVNS1ABP to actin and actin-associated proteins and dysregulated actin dynamics during cytokinesis. Taken together, we propose that IVNS1ABP mutation dysregulates actin polymerization and organization which is at least partly responsible for the cellular senescence phenotypes in this undiagnosed disease.

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