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Series GSE109269 Query DataSets for GSE109269
Status Public on Jan 17, 2018
Title Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4
Platform organism Homo sapiens
Sample organism Mus musculus
Experiment type Other
Summary Obesity, a prevalent condition in adults and children, impairs bone marrow (BM) function. However, the underlying mechanisms are unclear. Here we show that obese mice exhibit poor emergency immune responses in a toll-like receptor 4 (TLR4)-dependent manner. Canonical myeloid genes (Csf1r, Spi1, Runx1) are enhanced, and lymphoid genes (Flt3, Tcf3, Ebf1) are reduced. Using adoptive transfer and mixed BM chimera approaches we demonstrate that myeloid>lymphoid bias arises after six weeks of high fat diet and depends on precursor cell-autonomous TLR4. Further, lean mice exposed to the TLR4 ligand lipopolysaccharide (LPS) at doses similar to that detectable in obese serum recapitulates BM lympho-myeloid alterations. Together, these results establish a mechanistic contribution of BM cell-intrinsic TLR4 to obesity-driven BM malfunction and demonstrate the importance of LPS. Our findings raises important questions about the impact of maternal obesity and endotoxemia to fetal hematopoiesis, as fetal immune precursors are also sensitive to TLR4 signals.
Overall design Bone marrow lymphoid progenitors (CLP) as well as myeloid progenitors (LKSneg) sorted from mice fed high fat or control diet for 20 weeks were analyzed by transcriptional profiling.
Contributor(s) Liu A, Chen M, Kumar R, Stefanovic-Racic M, O'Doherty R, Ding Y, Jahnen-Dechent W, Borghesi L
Citation(s) 29453396
Submission date Jan 16, 2018
Last update date Apr 18, 2018
Contact name Lisa Ann Borghesi
Phone 412-383-9737
Organization name University of Pittsburgh
Department Immunology
Street address 200 Lothrop ST
City Pittsburgh
State/province PA
ZIP/Postal code 15261
Country USA
Platforms (1)
GPL24518 NanoString nCounter custom lympho-myeloid gene set (150)
Samples (11)
GSM2936321 NCD 1 CLP
GSM2936322 NCD 2 CLP
GSM2936323 NCD 3 CLP
BioProject PRJNA430266

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE109269_NCD_HFD_20wks_LKS-_normalization_data_exclude_one_sample.xlsx 22.1 Kb (ftp)(http) XLSX
GSE109269_NCD_HFD_CLPs_normalized_expression_data.xlsx 23.0 Kb (ftp)(http) XLSX
GSE109269_RAW.tar 40.0 Kb (http)(custom) TAR (of RCC)
Processed data included within Sample table
Processed data are available on Series record

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