|
| Status |
Public on Oct 08, 2019 |
| Title |
Liver-derived signals sequentially reprogram myeloid enhancers to initiate and maintain Kupffer cell identity (ChIP-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Tissue environment plays a powerful role in establishing and maintaining the distinct phenotypes of resident macrophages, but the underlying molecular mechanisms remain poorly understood. Here, we characterized transcriptomic and epigenetic changes in repopulating liver macrophages following acute Kupffer cell depletion as a means to infer signaling pathways and transcription factors that promote Kupffer cell differentiation. We obtain evidence that combinatorial interactions of the Notch ligand DLL4 and transforming growth factor-b (TGF-β) family ligands produced by sinusoidal endothelial cells and endogenous LXR ligands were required for the induction and maintenance of Kupffer cell identity. DLL4 regulation of the Notch transcriptional effector RBPJ activated poised enhancers to rapidly induce LXRα and other Kupffer cell lineage-determining factors. These factors in turn reprogrammed the repopulating liver macrophage enhancer landscape to converge on that of the original resident Kupffer cells. Collectively, these findings provide a framework for understanding how macrophage progenitor cells acquire tissue-specific phenotypes.
|
| |
|
| Overall design |
H3K27ac ChIP-seq for Blood Ly6C high monocytes from C57BL/6J mice; RLMs (repopulating liver macrophages) and Kupffer cells from Clec4f-Cre/DTR mice; BMDMs (bone marow-derived macrophages) from C57BL/6J mice stimulated with or without DLL4. SMAD4 ChIP-seq for Kupffer cell nuclei from Clec4f-cre mice or BMDMs from C57BL/6J mice. RBPJ ChIP-seq for Kupffer cell nuclei from Clec4f-cre mice or BMDMs from C57BL/6J mice.
|
| |
|
| Contributor(s) |
Sakai M, Troutman TD, Seidman JS, Ouyang Z, Spann NJ, Abe Y, Ego KM, Bruni CM, Schlachetzki JM, Nott A, Bennett H, Chang J, Vu BT, Pasillas MP, Link VM, Texari L, Heinz S, Thompson BM, McDonald JG, Geissmann F, Glass CK |
| Citation(s) |
31587991 |
| Submission date |
Mar 21, 2019 |
| Last update date |
Oct 08, 2019 |
| Contact name |
Christopher K Glass |
| E-mail(s) |
ckg@ucsd.edu
|
| Organization name |
University of California, San Diego
|
| Department |
School of Medicine
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (34)
|
|
| This SubSeries is part of SuperSeries: |
| GSE128662 |
Liver-derived signals sequentially reprogram myeloid enhancers to initiate and maintain Kupffer cell identity |
|
| Relations |
| BioProject |
PRJNA528437 |
| SRA |
SRP189059 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128658_ChIP_LXR_BMDM_GW3965_rep1.peak.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_LXR_BMDM_GW3965_rep2.peak.txt.gz |
857.5 Kb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_LXR_KC_notx_rep1.peak.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_LXR_KC_notx_rep2.peak.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_RBPJ_BMDM_notx_rep1.peak.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_RBPJ_BMDM_notx_rep2.peak.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_RBPJ_KcNuclei_notx_rep1.peak.txt.gz |
328.4 Kb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_RBPJ_KcNuclei_notx_rep2.peak.txt.gz |
279.0 Kb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_SMAD4_BMDM_notx_rep1.peak.txt.gz |
949.9 Kb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_SMAD4_BMDM_notx_rep2.peak.txt.gz |
755.7 Kb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_SMAD4_KcNuclei_notx_rep1.peak.txt.gz |
924.5 Kb |
(ftp)(http) |
TXT |
| GSE128658_ChIP_SMAD4_KcNuclei_notx_rep2.peak.txt.gz |
682.1 Kb |
(ftp)(http) |
TXT |
| GSE128658_DLL_allRawTags.txt.gz |
8.8 Mb |
(ftp)(http) |
TXT |
| GSE128658_DT_allRawTags.txt.gz |
8.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...