Gene expression and chromatin accessibility comparison in iPSC-derived microglia in African, European, and Amerindian genomes in Alzheimer's patients and controls.
Gene expression and chromatin accessibility comparison in iPSC-derived microglia in African, European, and Amerindian genomes in Alzheimer's patients and controls.
Alzheimer's disease (AD) risk differs between population groups, with African Americans and Hispanics being the most affected groups compared to non-Hispanic Whites. Genetic factors contribute significant risk to AD, but the genetic regulatory architectures (GRA) have primarily been studied in Europeans. Many AD genes are expressed in microglia; thus, we explored the impact of genetic ancestry (Amerindian (AI), African (AF), and European (EU)) on the GRA in iPSC-derived microglia from 13 individuals (~4 each with high global ancestry, AD and controls) through ATAC-seq and RNA-seq analyses. We identified several differentially accessible and expressed genes (2 and 10 AD-related, respectively) between ancestry groups. We also found a high correlation between the transcriptomes of iPSC-derived and brain microglia, supporting their use in human studies. This study provides valuable insights into genetically diverse microglia beyond the analysis of AD.
Starks Takiyah Diana、Adams Larry Deon、Griswold Anthony J、Byrd Goldie Smith、Feliciano-Astacio Briseida E、Rajabli Farid、Ramirez Aura Maria、Young Juan Isaac、Vance Jeffery Marvin、Wang Liyong、Coombs Lauren、Cornejo-Olivas Mario R、Dykxhoorn Derek M、Moura Sofia、Hamilton-Nelson Kara L、Nuytemans Karen、Tejada Sergio、Illanes-Manrique Maryenela、Mena Pedro Ramon、Nasciben Luciana Bertholim、Pericak-Vance Margaret A、Rivero Joe、DeRosa Brooke Alisen、Van Booven Derek J、Whitehead Patrice L
基础医学遗传学神经病学、精神病学
Starks Takiyah Diana,Adams Larry Deon,Griswold Anthony J,Byrd Goldie Smith,Feliciano-Astacio Briseida E,Rajabli Farid,Ramirez Aura Maria,Young Juan Isaac,Vance Jeffery Marvin,Wang Liyong,Coombs Lauren,Cornejo-Olivas Mario R,Dykxhoorn Derek M,Moura Sofia,Hamilton-Nelson Kara L,Nuytemans Karen,Tejada Sergio,Illanes-Manrique Maryenela,Mena Pedro Ramon,Nasciben Luciana Bertholim,Pericak-Vance Margaret A,Rivero Joe,DeRosa Brooke Alisen,Van Booven Derek J,Whitehead Patrice L.Gene expression and chromatin accessibility comparison in iPSC-derived microglia in African, European, and Amerindian genomes in Alzheimer's patients and controls.[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2024.08.27.609943.点此复制
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