Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.

Autor:	Pintacuda G; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA., Hsu YH; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA., Tsafou K; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA., Li KW; Department of Molecular and Cellular Neurobiology, CNCR, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands., Martín JM; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA., Riseman J; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA., Biagini JC; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Ching JKT; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Mena D; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Gonzalez-Lozano MA; Department of Molecular and Cellular Neurobiology, CNCR, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands., Egri SB; Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Jaffe J; Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Smit AB; Department of Molecular and Cellular Neurobiology, CNCR, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands., Fornelos N; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA., Eggan KC; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA., Lage K; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, 4000 Roskilde, Denmark.
Jazyk:	angličtina
Zdroj:	Cell genomics [Cell Genom] 2023 Jan 24; Vol. 3 (3), pp. 100250. Date of Electronic Publication: 2023 Jan 24 (Print Publication: 2023).
DOI:	10.1016/j.xgen.2022.100250
Abstrakt:	Autism spectrum disorders (ASDs) have been linked to genes with enriched expression in the brain, but it is unclear how these genes converge into cell-type-specific networks. We built a protein-protein interaction network for 13 ASD-associated genes in human excitatory neurons derived from induced pluripotent stem cells (iPSCs). The network contains newly reported interactions and is enriched for genetic and transcriptional perturbations observed in individuals with ASDs. We leveraged the network data to show that the ASD-linked brain-specific isoform of ANK2 is important for its interactions with synaptic proteins and to characterize a PTEN-AKAP8L interaction that influences neuronal growth. The IGF2BP1-3 complex emerged as a convergent point in the network that may regulate a transcriptional circuit of ASD-associated genes. Our findings showcase cell-type-specific interactomes as a framework to complement genetic and transcriptomic data and illustrate how both individual and convergent interactions can lead to biological insights into ASDs. Competing Interests: K.C.E. is a co-founder of Q-State Biosciences, Quralis, and Enclear and is currently employed at BioMarin Pharmaceutical. (© 2023 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu