@article{TEXTUAL,
      recid = {1930},
      author = {Butler III, Robert R. and Kozlova, Alena and Zhang, Hanwen  and Zhang, Siwei and Streit, Michael and Sanders, Alan R.  and Laudanski, Krzysztof and Pang, Zhiping P. and Gejman,  Pablo V. and Duan, Jubao},
      title = {The genetic relevance of human iPSC-derived microglia to  Alzheimer’s disease and major neuropsychiatric disorders},
      journal = {Molecular Neuropsychiatry},
      address = {2019-07-23},
      number = {TEXTUAL},
      abstract = {Microglia are the primary innate immune cell type in the  brain that have been implicated in the pathogenesis of  several neurodegenerative and neuropsychiatric disorders,  most notably Alzheimer’s disease (AD) and schizophrenia.  Microglia generated from human induced pluripotent stem  cells (hiPSCs) represent a promising in vitro cellular  model for studying the neuroimmune interactions involved in  these disorders. Among several methods of generating  ­hiPSC-derived microglia (iMG) – varying in duration and  resultant purity – a recent protocol by Brownjohn et al.  [Stem Cell Reports. 2018 Apr;10(4):1294–307] is  particularly simple and efficient. However, the  replicability of this method, transcriptomic similarity of  these iMG to primary adult microglia, and their genetic  relevance to disease (i.e., enrichment of disease risk loci  in genes preferentially expressed in these cells) remains  unclear. Using two hiPSC lines, we demonstrated that  Brownjohn’s protocol can rapidly generate iMG that  morphologically and functionally resembled microglia. The  iMG cells we generated were found to be transcriptionally  similar to previously reported iMG, as well as fetal and  adult microglia. Furthermore, by using cell type-specific  gene expression to partition disease heritability, we  showed that iMG cells are genetically relevant to AD but  found no significant enrichments of risk loci of  Parkinson’s disease, schizophrenia, major depressive  disorder, bipolar disorder, autism spectrum disorder, or  body mass index. Across a range of neuronal and immune cell  types, we found only iMG, primary microglia, and  microglia-like cell types exhibited a significant  enrichment for AD heritability. Our results thus support  the use of iMG as a human cellular model for understanding  AD biology and underlying genetic factors, as well as for  developing and efficiently screening new therapeutics.},
      url = {http://knowledge.uchicago.edu/record/1930},
}