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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
borghesi@pitt.edu
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| Phone |
412-383-9737
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| Organization name |
University of Pittsburgh
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| Department |
Immunology
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| Street address |
200 Lothrop ST
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15261 |
| Country |
USA |
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| Platforms (1) |
| GPL24518 |
NanoString nCounter custom lympho-myeloid gene set (150) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA430266 |
| 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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