期刊
STEM CELL REPORTS
卷 14, 期 4, 页码 703-716出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2020.02.010
关键词
-
资金
- National Institute of Neurological Disorders and Stroke [R21 NS107594 02]
- Penn Center for Aids Research (CFAR) [5-P30-MH-097488-05]
- Penn Mental Health AIDS Research Center (PMHARC) [5-P30-MH-097488-05]
- Intellectual and Developmental Disabilities Research Center at CHOP/Penn [U54 HD086984]
HIV-associated neurocognitive disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a representative model. We developed a human-induced pluripotent stem cell (hiPSC)-based model, independently differentiating hiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV infection and ART. Single-cell RNA sequencing analysis on tricultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound efavirenz (EFZ) mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in transforming growth factor alpha production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据