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| Status |
Public on Nov 17, 2011 |
| Title |
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA (siRNA) targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-kappaB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD.
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| Overall design |
The siRNA vector construct targeting the DAP12 sequence (SI) and the control vector construct targeting the scrambled sequence (SCR) were generated by using GeneClip U1 Hairpin cloning system (Promega). The vectors were transfected in THP-1 cells by using Lipofectamine LTX reagent. The stable cell lines were selected by incubating them for approximately two months in the feeding medium with inclusion of 200 microgram/ml Hygromycin B. Then, two SI clones named SI5 and SI17, in addition to two SCR clones named SCR1 and SCR4, were selected by limiting dilution of the cells in a manner of a single cell per well plated in a 96-well cell culture plate.
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| Contributor(s) |
Satoh J, Shimamura Y, Tabunoki H |
| Citation(s) |
22080356 |
| Submission date |
Nov 06, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Jun-ichi Satoh |
| E-mail(s) |
satoj@my-pharm.ac.jp
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| Organization name |
Meiji Pharmaceutical University
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| Department |
Bioinformatics
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| Lab |
Molecular Neuropathology
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| Street address |
2-522-1 Noshio, Kiyose
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| City |
Tokyo |
| ZIP/Postal code |
204-8588 |
| Country |
Japan |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (3) |
| GSM828762 |
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease (I) |
| GSM828763 |
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease (II) |
| GSM828764 |
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease (III) |
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| Relations |
| BioProject |
PRJNA148849 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33500_RAW.tar |
13.7 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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