Vasan, Lakshmy, Chinchalongporn, Vorapin, Saleh, Fermisk, Zinyk, Dawn, Ke, Cao, Suresh, Hamsini, Ghazale, Hussein, Belfiore, Lauren, Touahri, Yacine, Oproescu, Ana-Maria, Patel, Shruti, Rozak, Matthew, Amemiya, Yutaka, Han, Sisu, Moffat, Alexandra, Black, Sandra E, McLaurin, JoAnne, Near, Jamie, Seth, Arun, Goubran, Maged, Reiner, Orly, Gillis, Jesse, Wang, Chao, Okawa, Satoshi, Schuurmans, Carol (January 2025) Examining the NEUROG2 lineage and associated gene expression in human cortical organoids. Development, 152 (2). dev.202703. ISSN 0950-1991 (Public Dataset)
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Abstract
Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated from human embryonic stem cell-derived cortical organoids (COs) to show that NEUROG1 and NEUROG2 are most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating that NEUROG1-derived lineages predominate early and NEUROG2 lineages later. Using ChIP-qPCR, gene silencing and overexpression studies in COs, we show that NEUROG2 is necessary and sufficient to directly transactivate known target genes (NEUROD1, EOMES, RND2). To identify new targets, we engineered NEUROG2-mCherry knock-in human embryonic stem cells for CO generation. The mCherry-high CO cell transcriptome is enriched in extracellular matrix-associated genes, and two genes associated with human-accelerated regions: PPP1R17 and FZD8. We show that NEUROG2 binds COL1A1, COL3A1 and PPP1R17 regulatory elements, and induces their ectopic expression in COs, although NEUROG2 is not required for this expression. Neurog2 similarly induces Col3a1 and Ppp1r17 in murine P19 cells. These data are consistent with a conservation of NEUROG2 function across mammalian species.
| Item Type: | Paper |
|---|---|
| Subjects: | Investigative techniques and equipment Investigative techniques and equipment > cell culture > cancer organoids Investigative techniques and equipment > cell culture Investigative techniques and equipment > cell lineage tracing |
| CSHL Authors: | |
| Communities: | CSHL labs > Gillis Lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 15 January 2025 |
| Date Deposited: | 18 Mar 2025 12:12 |
| Last Modified: | 18 Mar 2025 12:12 |
| PMCID: | PMC11829764 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/41823 |
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