| First Author | Tangeman JA | Year | 2024 |
| Journal | Development | Volume | 151 |
| Issue | 1 | PubMed ID | 38180241 |
| Mgi Jnum | J:344241 | Mgi Id | MGI:7574182 |
| Doi | 10.1242/dev.202249 | Citation | Tangeman JA, et al. (2024) Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology. Development 151(1):dev202249 |
| abstractText | Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataracts. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq and CUT&RUN-seq to discover previously unreported mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Furthermore, we identify an epigenetic paradigm of cellular differentiation, defined by progressive loss of the H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation. |
