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RNA-seq profiling of iPSC-derived microglia (iMicroglia) with wild-type or GPNMB knockout genotype

ABSTRACT: Glycoprotein nonmetastatic melanoma B (GPNMB) is critical to cellular uptake of pathological forms of alpha-synuclein (aSyn), the hallmark disease protein in Parkinson's Disease (PD). Here, we demonstrate that the non-membrane-anchored, extracellular domain of GPNMB can function in a non-cell-autonomous manner. In human brain, GPNMB is widely expressed in neurons and microglia. In induced pluripotent stem cell-derived microglia (iMicroglia), GPNMB expression and secretion increase with exposure to apoptotic neurons. In the aSyn fibril-seeded model of PD, iMicroglia-derived GPNMB enhances neuronal aSyn uptake and development of aSyn pathology, including in GPNMB knockout neurons. This dataset contains bulk RNA-seq data from iPSC-derived microglia (iMicroglia) differentiated using the Brownjohn protocol from isogenic GPNMB wild-type (WT) and GPNMB knockout (KO) iPSC lines (3 biological replicates each), treated with PBS as vehicle control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE328042 | GEO | 2026/05/06

REPOSITORIES: GEO

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GPNMB confers risk for Parkinson’s disease through interaction with alpha-synuclein

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