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| Status |
Public on Jul 23, 2024 |
| Title |
Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration [RNA-seq: wildtype_EMCN] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48−LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN− LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN− LT-HSCs. Emcn−/− and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn−/− LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn−/− or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant.
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| Overall design |
RNA was isolated from 3000-5000 FACS sorted EMCN+CD150+CD48-LSK (EMCN+ LT-HSCs) and EMCN-CD150+CD48-LSK (EMCN- LT-HSCs) for RNA sequencing. Granulocyte-Monocyte progenitors (GMPs) were additionally sorted as well characterised population to serve as more differentiated population for comparison. BM cells were isolated from C57Bl6 mice purchased at Taconic (Denmark). 4 biological replicates for each population, one EMCN-LT-HSC replicate was removed from analysis due to poor quality of the sequenced library.
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| Contributor(s) |
Engelhard S, Estruch Alrich M, Qin S, Engelhard CA, Rodriguez-Gonzalez FG, Drilsvik M, Martin-Gonzalez J, Lu J, Bryder D, Nerlov C, Weischenfeldt J, Reckzeh K, Theilgaard-Mönch K |
| Citation(s) |
38996072 |
| |
| Submission date |
Jan 16, 2023 |
| Last update date |
Jul 23, 2024 |
| Contact name |
Kim Theilgaard-Mönch |
| E-mail(s) |
[email protected]
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| Organization name |
University of Copenhagen & Rigshospitalet/National University hospital
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| Department |
BRIC & The Finsen Laboratory
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| Street address |
Ole maaløes vej 5
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| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (11)
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| This SubSeries is part of SuperSeries: |
| GSE222943 |
Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration |
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| Relations |
| BioProject |
PRJNA924266 |
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