Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
04 03 2022
Historique:
entrez: 4 3 2022
pubmed: 5 3 2022
medline: 20 4 2022
Statut: ppublish

Résumé

Schizophrenia (SCZ) is a chronic, serious mental disorder. Although more than 200 SCZ-associated genes have been identified, the underlying molecular and cellular mechanisms remain largely unknown. Here, we generated a Setd1a (SET domain containing 1A) haploinsufficiency mouse model to understand how this SCZ-associated epigenetic factor affects gene expression in brain regions highly relevant to SCZ. Single-cell RNA sequencing revealed that Setd1a heterozygosity causes highly variable transcriptional adaptations across different cell types in prefrontal cortex (PFC) and striatum. The

Identifiants

pubmed: 35245111
doi: 10.1126/sciadv.abm1077
pmc: PMC8896793
doi:

Substances chimiques

Histone-Lysine N-Methyltransferase EC 2.1.1.43
Nsccn1 protein, mouse EC 2.1.1.43
Setd1A protein, human EC 2.1.1.43

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabm1077

Subventions

Organisme : NIDA NIH HHS
ID : R01 DA042283
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA050589
Pays : United States

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Auteurs

Renchao Chen (R)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Yiqiong Liu (Y)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Mohamed N Djekidel (MN)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Wenqiang Chen (W)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Aritra Bhattacherjee (A)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Zhiyuan Chen (Z)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.

Ed Scolnick (E)

The Stanley Center for Psychiatric Research at Broad Institute, Cambridge, MA 02142, USA.

Yi Zhang (Y)

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Harvard Stem Cell Institute, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA.

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Classifications MeSH