TY - JOUR
T1 - Cortical cellular diversity and development in schizophrenia
AU - Price, Amanda J.
AU - Jaffe, Andrew E.
AU - Weinberger, Daniel R.
N1 - Funding Information:
Funding This work is supported by the generous donations of the Lieber and Maltz families. In addition, AJP was supported by R21MH105853, R01MH112751, and U01MH106893; AEJ was supported by R21MH105853 and R01MH112751; and DRW was supported by R21MH105853 and U01MH106893.
Publisher Copyright:
© 2020, Springer Nature Limited.
PY - 2021/1
Y1 - 2021/1
N2 - While a definitive understanding of schizophrenia etiology is far from current reality, an increasing body of evidence implicates perturbations in early development that alter the trajectory of brain maturation in this disorder, leading to abnormal function in early childhood and adulthood. This atypical development likely arises from an interaction of many brain cell types that follow distinct developmental paths. Because both cellular identity and development are governed by the transcriptome and epigenome, two levels of gene regulation that have the potential to reflect both genetic and environmental influences, mapping “omic” changes over development in diverse cells is a fruitful avenue for schizophrenia research. In this review, we provide a survey of human brain cellular composition and development, levels of genomic regulation that determine cellular identity and developmental trajectories, and what is known about how genomic regulation is dysregulated in specific cell types in schizophrenia. We also outline technical challenges and solutions to conducting cell type-specific functional genomic studies in human postmortem brain.
AB - While a definitive understanding of schizophrenia etiology is far from current reality, an increasing body of evidence implicates perturbations in early development that alter the trajectory of brain maturation in this disorder, leading to abnormal function in early childhood and adulthood. This atypical development likely arises from an interaction of many brain cell types that follow distinct developmental paths. Because both cellular identity and development are governed by the transcriptome and epigenome, two levels of gene regulation that have the potential to reflect both genetic and environmental influences, mapping “omic” changes over development in diverse cells is a fruitful avenue for schizophrenia research. In this review, we provide a survey of human brain cellular composition and development, levels of genomic regulation that determine cellular identity and developmental trajectories, and what is known about how genomic regulation is dysregulated in specific cell types in schizophrenia. We also outline technical challenges and solutions to conducting cell type-specific functional genomic studies in human postmortem brain.
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U2 - 10.1038/s41380-020-0775-8
DO - 10.1038/s41380-020-0775-8
M3 - Review article
C2 - 32404946
AN - SCOPUS:85084439596
VL - 26
SP - 203
EP - 217
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 1
ER -