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Series GSE139336 Query DataSets for GSE139336
Status Public on Jan 03, 2020
Title Prospective isolation of radiation induced erythroid stress progenitors reveals unique transcriptomic and epigenetic signatures enabling increased erythroid output
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Massive expansion of erythroid progenitor cells is essential for surviving anemic stress. Research towards understanding this critical process, referred to as stress-erythropoiesis, has been hampered due to lack of specific marker-combinations enabling analysis of the distinct stress-progenitor cells capable of providing radioprotection and enhanced red blood cell production. Here we present a method for precise identification and in vivo validation of progenitor cells contributing to both steady-state and stress-erythropoiesis, enabling for the first time in-depth molecular characterization of these cells. Differential expression of surface markers CD150, CD9 and Sca1 defines a hierarchy of splenic stress-progenitors during irradiation-induced stress recovery in mice, and provides high-purity isolation of the functional stress-BFU-Es with a 100-fold improved enrichment compared to state-of-the-art. By transplanting purified stress-progenitors expressing the fluorescent protein Kusabira Orange, we have for the first time determined their kinetics in vivo and demonstrated that CD150+CD9+Sca1- stress-BFU-Es provide a massive but transient radioprotective erythroid wave, followed by multi-lineage reconstitution from CD150+CD9+Sca1+ multi-potent stem/progenitor cells. Whole genome transcriptional analysis revealed that stress-BFU-Es express gene signatures more associated with erythropoiesis and proliferation compared to steady-state BFU-Es, and are BMP-responsive. Evaluation of chromatin accessibility through ATAC sequencing reveals enhanced and differential accessibility to binding sites of the chromatin-looping transcription factor CTCF in stress-BFU-Es compared to steady-state BFU-Es. Our findings offer molecular insight to the unique capacity of stress-BFU-Es to rapidly form erythroid cells in response to anemia and constitute an important step towards identifying novel erythropoiesis stimulating agents.
Overall design For RNA-seq, one steady-state BFU-E population in bone marrow and one from irradiation-induced stress erythropoiesis in spleen were sorted and sequenced in triplicates together with one stressed splenic MPP and one CFU-E population for internal comparison. For ATAC-seq, one steady-state BFU-E population in bone marrow and one from irradiation-induced stress erythropoiesis in spleen were sorted and sequenced in triplicates.
Contributor(s) Singbrant S, Mattebo A, Strid T, Sigvardsson M, Flygare J
Citation(s) 33131245
Submission date Oct 24, 2019
Last update date Mar 01, 2021
Contact name Johan Flygare
Organization name Lund University
Lab Flygare
Street address Sölvegatan 19
City Lund
ZIP/Postal code 22184
Country Sweden
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (18)
GSM4138346 ATAC-seq-Spleen-Sca-neg-#1
GSM4138347 ATAC-seq-Spleen-Sca-neg-#2
GSM4138348 ATAC-seq-Spleen-Sca-neg-#3
BioProject PRJNA579342
SRA SRP226834

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

Supplementary file Size Download File type/resource
GSE139336_AnalyzeRepeats-BM-and-Spleen-samples-Sca-neg_Sca-pos_CD9-neg_count-exons_condeseGenes_rpkm.txt.gz 1.5 Mb (ftp)(http) TXT
GSE139336_AnalyzeRepeats-Spleen-samples-Sca-neg_Sca-pos_CD9-neg_count-exons_condeseGenes_noadj.txt.gz 1.2 Mb (ftp)(http) TXT
GSE139336_AnalyzeRepeats-mm10-count-exons-condenseGenes-noadj-BM-Sca-neg-Spleen-Sca-neg-filtered-on-mean50tags.txt.gz 596.8 Kb (ftp)(http) TXT
GSE139336_AnalyzeRepeats-mm10-count-exons-condenseGenes-rpkm-BM-Sca-neg-Spleen-Sca-neg.txt.gz 1.2 Mb (ftp)(http) TXT
GSE139336_BM-idr-ATAC-peaks-annotated-mm10.txt.gz 4.2 Mb (ftp)(http) TXT
GSE139336_Spleen-idr-ATAC-peaks-annotated-mm10.txt.gz 7.7 Mb (ftp)(http) TXT
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