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GEO help: Mouse over screen elements for information. |
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Status |
Public on Oct 31, 2023 |
Title |
Functional and molecular profiling of hematopoietic stem cells during regeneration |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Hematopoietic stem cells (HSCs) enable hematopoietic stem cell transplantation (HCT) through their ability to replenish the entire blood system. Proliferation of HSCs is linked to decreased reconstitution potential, and a precise regulation of actively dividing HSCs is thus essential to ensure long-term functionality. This regulation becomes important in the transplantation setting where HSCs undergo proliferation followed by a gradual transition to quiescence and homeostasis. While mouse HSCs have been well studied during homeostatic conditions, the mechanisms regulating HSC activation during stress remain unclear. Here, we analyzed the different phases of regeneration following transplantation. We isolated bone marrow from mice at eight time points after transplantation and examined the reconstitution dynamics and transcriptional profiles of stem and progenitor populations. We found that regenerating HSCs initially produced rapidly expanding progenitors and displayed distinct changes in fatty acid metabolism and glycolysis. Moreover, we observed molecular changes in cell cycle, MYC and mTOR signaling in both HSCs and the progenitor subsets. We used a decay rate model to fit the temporal transcription profiles of regenerating HSCs and identified genes with progressively decreased or increased expression after transplantation. These genes overlapped to a large extent with published gene sets associated with key aspects of HSC function demonstrating the potential of this data set as a resource for identification of novel HSC regulators. Taken together, our study provides a detailed functional and molecular characterization of HSCs at different phases of regeneration and identifies a gene set associated with the transition from proliferation to quiescence.
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Overall design |
RNAseq of steady state HSCs and HSCs isolated 3, 4, 5, 6, 8, 10, 13, and 16 weeks after transplantation.
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Contributor(s) |
Rydström A, Grahn TH, Niroula A, Mansell E, van der Garde M, Pertesi M, Subramaniam A, Soneji S, Zubarev R, Enver T, Nilsson B, Miharada K, Larsson J, Karlsson S |
Citation(s) |
37666355 |
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Submission date |
Aug 17, 2023 |
Last update date |
Oct 31, 2023 |
Contact name |
Maroulio Pertesi |
Organization name |
Lund University
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Street address |
Sölvegatan 19
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City |
Lund |
ZIP/Postal code |
22184 |
Country |
Sweden |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (95)
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Relations |
BioProject |
PRJNA1006383 |
Supplementary file |
Size |
Download |
File type/resource |
GSE241088_raw_counts_allSample_withMGI.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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