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| Status |
Public on Apr 27, 2023 |
| Title |
Stem cell decoupling underlies impaired lymphoid development during aging [scATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mammalian aging is associated with multiple defects of hematopoiesis, most prominently with the impaired development of T and B lymphocytes. This defect is thought to originate in hematopoietic stem cells (HSCs) of the bone marrow, specifically due to the age-dependent accumulation of HSCs with preferential megakaryocytic and/or myeloid potential ("myeloid bias"). Here we tested this notion used inducible genetic labeling and tracing of HSCs in unmanipulated animals. We found that the endogenous HSC population in old mice shows reduced differentiation into all lineages including lymphoid, myeloid and megakaryocytic. Single-cell RNA sequencing and immunophenotyping (CITE-Seq) showed that HSC progeny in old animals comprised balanced lineage spectrum including lymphoid progenitors. Lineage tracing using the aging-induced HSC marker Aldh1a1 confirmed the low contribution of old HSCs across all lineages. Competitive transplantations of total bone marrow cells with genetically marked HSCs revealed that the contribution of old HSCs was reduced, but compensated by other donor cells in myeloid cells but not in lymphocytes. Thus, the HSC population in old animals becomes globally decoupled from hematopoiesis, which cannot be compensated in lymphoid lineages. We propose that this partially compensated decoupling, rather than myeloid bias, is the primary cause of the selective impairment of lymphopoiesis in the old age.
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| Overall design |
Two old (20 months)Pdzk1ip1-CreER R26Tom/Tommice were induced with 1mg of tamoxifen. After 7 days post-induction Lin- Sca-1+ c-Kit+ CD150+ CD48- HSCs (entire HSC population) were sorted and pooled. Note that tdTomato expression was not used for sorting, but tamoxifen-induced mice were used for consistency with other experiments.
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| Contributor(s) |
Jang G, Contreras Castillo S, Esteva E, Upadhaya S, Feng J, Adams NM, Richard E, Awatramani R, Sawai CM, Reizis B |
| Citation missing |
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| Submission date |
Apr 04, 2023 |
| Last update date |
Apr 28, 2023 |
| Contact name |
Stephania Contreras Castillo |
| Organization name |
Université de Bordeaux
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| Street address |
2, Docteur Hoffman Martinot
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| City |
Bordeaux |
| ZIP/Postal code |
33000 |
| Country |
France |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE229018 |
Stem cell decoupling underlies impaired lymphoid development during aging |
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| Relations |
| BioProject |
PRJNA952226 |
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