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| Status |
Public on Oct 01, 2018 |
| Title |
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways
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| Overall design |
CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;
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| Contributor(s) |
Leaf I, Puranik AS, Lerman LO |
| Citation(s) |
30224726 |
| Submission date |
Jun 20, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Lilach Lerman |
| Organization name |
Mayo Clinic
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| Street address |
200 1st St SW
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| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (21)
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| GSM3229997 |
MPC1SHAM1: CD11cHI macrophages from sham kidneys |
| GSM3229998 |
MPC1SHAM2: CD11cHI macrophages from sham kidneys |
| GSM3229999 |
MPC1SHAM3: CD11cHI macrophages from sham kidneys |
| GSM3230000 |
MPC1RAS1: CD11cHI macrophages from RAS kidneys |
| GSM3230001 |
MPC1RAS2: CD11cHI macrophages from RAS kidneys |
| GSM3230002 |
MPC1RAS3: CD11cHI macrophages from RAS kidneys |
| GSM3230003 |
MPC1RAS4: CD11cHI macrophages from RAS kidneys |
| GSM3230004 |
MPC2SHAM1: CD11cLO macrophages from sham kidneys |
| GSM3230005 |
MPC2SHAM2: CD11cLO macrophages from sham kidneys |
| GSM3230006 |
MPC2SHAM3: CD11cLO macrophages from sham kidneys |
| GSM3230007 |
MPC2RAS1: CD11cLO macrophages from RAS kidneys |
| GSM3230008 |
MPC2RAS2: CD11cLO macrophages from RAS kidneys |
| GSM3230009 |
MPC2RAS3: CD11cLO macrophages from RAS kidneys |
| GSM3230010 |
MPC2RAS4: CD11cLO macrophages from RAS kidneys |
| GSM3230011 |
MPC3SHAM1: Kidney resident macrophages (KRM) from sham kidneys |
| GSM3230012 |
MPC3SHAM2: Kidney resident macrophages (KRM) from sham kidneys |
| GSM3230013 |
MPC3SHAM3: Kidney resident macrophages (KRM) from sham kidneys |
| GSM3230014 |
MPC3SHAM4: Kidney resident macrophages (KRM) from sham kidneys |
| GSM3230015 |
MPC3RAS1: Kidney resident macrophages (KRM) from RAS kidneys |
| GSM3230016 |
MPC3RAS2: Kidney resident macrophages (KRM) from RAS kidneys |
| GSM3230017 |
MPC3RAS3: Kidney resident macrophages (KRM) from RAS kidneys |
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| Relations |
| BioProject |
PRJNA478258 |
| SRA |
SRP151504 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116094_KRM_RAS_GeneOntologyAnalysis.xlsx |
73.4 Kb |
(ftp)(http) |
XLSX |
| GSE116094_KRM_RawCounts.txt.gz |
964.3 Kb |
(ftp)(http) |
TXT |
| GSE116094_KRM_TPMnormalized.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE116094_KidneyResidentMacrophages_DEGs.xlsx |
598.8 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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