Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder.
Fuente:
PubMed
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
bioRxiv : the preprint server for biology
2026
|
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1868266059512938497 |
|---|---|
| author | Kim, Jonghun Choe, Mu Seog Kaya, Kutlu Hu, Yue Ng, Kenneth K Qiu, Caihong Zhong, Mei Yang, Woo Sub Kiral, Ferdi Ridvan Lo, Cynthia Scandura, Michael Cha, Hyuk-Jin Gruen, Jeffrey R Lek, Monkol Jonas, Elizabeth A Blumberg, Hilary P Park, In-Hyun |
| author_facet | Kim, Jonghun Choe, Mu Seog Kaya, Kutlu Hu, Yue Ng, Kenneth K Qiu, Caihong Zhong, Mei Yang, Woo Sub Kiral, Ferdi Ridvan Lo, Cynthia Scandura, Michael Cha, Hyuk-Jin Gruen, Jeffrey R Lek, Monkol Jonas, Elizabeth A Blumberg, Hilary P Park, In-Hyun Kim, Jonghun Choe, Mu Seog Kaya, Kutlu Hu, Yue Ng, Kenneth K Qiu, Caihong Zhong, Mei Yang, Woo Sub Kiral, Ferdi Ridvan Lo, Cynthia Scandura, Michael Cha, Hyuk-Jin Gruen, Jeffrey R Lek, Monkol Jonas, Elizabeth A Blumberg, Hilary P Park, In-Hyun |
| collection | PubMed - marine biology |
| contents | Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder. Kim, Jonghun Choe, Mu Seog Kaya, Kutlu Hu, Yue Ng, Kenneth K Qiu, Caihong Zhong, Mei Yang, Woo Sub Kiral, Ferdi Ridvan Lo, Cynthia Scandura, Michael Cha, Hyuk-Jin Gruen, Jeffrey R Lek, Monkol Jonas, Elizabeth A Blumberg, Hilary P Park, In-Hyun Bipolar disorder (BD) is a prevalent and highly heritable psychiatric condition. Developmental mechanisms are implicated but the specific molecular origins remain unclear. The choroid plexus (ChP), which regulates cerebrospinal fluid (CSF) and brain homeostasis, has been implicated in BD, but its role is poorly understood. Here, we identify aberrant expansion of ChP in human cortical (hCOs) and ChP organoids (hChPOs) derived from, and structural magnetic resonance imaging (sMRI) scans of, individuals with BD compared to healthy comparison individuals. Single-cell transcriptomics revealed a lineage bias toward ChP fate in BD hCOs, accompanied by structural enlargement observed in both BD hChPOs and ChP in sMRI scans from individuals with BD. Comprehensive transcriptomic profiling implicates early hyperactivation of the Hippo signaling pathway in neural progenitor cells as a convergent mechanism driving ChP overgrowth. Whole-genome and genome-wide association study analyses highlight recurrent genetic variants in Hippo regulators, including and , suggesting genetic priming. BD hChPOs exhibit disrupted epithelial junctions and altered CSF secretion. These findings position the ChP as a genetically and developmentally predisposed to pathology in BD and highlight organoids as a platform for translational discovery in diagnostics and therapeutics. |
| format | Artículo científico |
| id | pubmed_41993308 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | bioRxiv : the preprint server for biology |
| record_format | pubmed |
| spellingShingle | Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder. Kim, Jonghun Choe, Mu Seog Kaya, Kutlu Hu, Yue Ng, Kenneth K Qiu, Caihong Zhong, Mei Yang, Woo Sub Kiral, Ferdi Ridvan Lo, Cynthia Scandura, Michael Cha, Hyuk-Jin Gruen, Jeffrey R Lek, Monkol Jonas, Elizabeth A Blumberg, Hilary P Park, In-Hyun Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder. Kim, Jonghun Choe, Mu Seog Kaya, Kutlu Hu, Yue Ng, Kenneth K Qiu, Caihong Zhong, Mei Yang, Woo Sub Kiral, Ferdi Ridvan Lo, Cynthia Scandura, Michael Cha, Hyuk-Jin Gruen, Jeffrey R Lek, Monkol Jonas, Elizabeth A Blumberg, Hilary P Park, In-Hyun Bipolar disorder (BD) is a prevalent and highly heritable psychiatric condition. Developmental mechanisms are implicated but the specific molecular origins remain unclear. The choroid plexus (ChP), which regulates cerebrospinal fluid (CSF) and brain homeostasis, has been implicated in BD, but its role is poorly understood. Here, we identify aberrant expansion of ChP in human cortical (hCOs) and ChP organoids (hChPOs) derived from, and structural magnetic resonance imaging (sMRI) scans of, individuals with BD compared to healthy comparison individuals. Single-cell transcriptomics revealed a lineage bias toward ChP fate in BD hCOs, accompanied by structural enlargement observed in both BD hChPOs and ChP in sMRI scans from individuals with BD. Comprehensive transcriptomic profiling implicates early hyperactivation of the Hippo signaling pathway in neural progenitor cells as a convergent mechanism driving ChP overgrowth. Whole-genome and genome-wide association study analyses highlight recurrent genetic variants in Hippo regulators, including and , suggesting genetic priming. BD hChPOs exhibit disrupted epithelial junctions and altered CSF secretion. These findings position the ChP as a genetically and developmentally predisposed to pathology in BD and highlight organoids as a platform for translational discovery in diagnostics and therapeutics. |
| title | Dysregulation of Hippo Signaling Pathway as a Convergent Mechanism Underlying Choroid Plexus Defects in Bipolar Disorder. |
| url | https://pubmed.ncbi.nlm.nih.gov/41993308/ |