Examining the NEUROG2-lineage and associated-gene expression in human cortical organoids.

Autor:	Vasan L; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Chinchalongporn V; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Saleh F; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Zinyk D; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Ke C; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Immunology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Suresh H; Department of Physiology, University of Toronto, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, 160 College St, Toronto, ON M5S3E1, Canada., Ghazale H; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Belfiore L; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Touahri Y; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Oproescu AM; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Patel S; Department of Medical Biophysics, 101 College St Suite 15-701, Toronto General Hospital, University of Toronto, ON, M5G 1L7, Canada.; 8 Sunnybrook Research Institute, Physical Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada., Rozak M; Department of Medical Biophysics, 101 College St Suite 15-701, Toronto General Hospital, University of Toronto, ON, M5G 1L7, Canada.; 8 Sunnybrook Research Institute, Physical Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada., Amemiya Y; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Han S; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Moffat A; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Black SE; Dr. Sandra Black Centre for Brain Resilience & Recovery, LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Ontario; Hurvitz Brain Sciences Program, Canada.; Department of Medicine (Neurology) (SEB), University of Toronto, Toronto, Ontario, Canada., McLaurin J; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Near J; Department of Medical Biophysics, 101 College St Suite 15-701, Toronto General Hospital, University of Toronto, ON, M5G 1L7, Canada.; 8 Sunnybrook Research Institute, Physical Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada., Seth A; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Goubran M; Department of Medical Biophysics, 101 College St Suite 15-701, Toronto General Hospital, University of Toronto, ON, M5G 1L7, Canada.; 8 Sunnybrook Research Institute, Physical Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada., Reiner O; Departments of Molecular Genetics and Molecular Neuroscience, Weizmann Institute of Science, 76100, Rehovot, Israel., Gillis J; Department of Physiology, University of Toronto, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, 160 College St, Toronto, ON M5S3E1, Canada., Wang C; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Immunology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada., Okawa S; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Schuurmans C; Sunnybrook Research Institute, Biological Sciences Platform, Hurvitz Brain Sciences Program, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.; Department of Biochemistry, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada.; Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King's College Cir, University of Toronto, ON, M5S 1A8, Canada.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Dec 16. Date of Electronic Publication: 2024 Dec 16.
DOI:	10.1242/dev.202703
Abstrakt:	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 (hESC)-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 NEUROG2 is necessary and sufficient to directly transactivate known target genes (NEUROD1, EOMES, RND2). To identify new targets, we engineered NEUROG2-mCherry knock-in hESCs for CO generation. The mCherry-high CO cell transcriptome is enriched in extracellular matrix (ECM)-associated genes, and two genes associated with human-accelerated regions; PPP1R17 and FZD8. We show 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. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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