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| Status |
Public on Apr 27, 2023 |
| Title |
Stem cell decoupling underlies impaired lymphoid development during aging [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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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 |
CITE-seq datasets: Lin-cKit+Tom+ and Lin-Flt3+Tom+ cells were isolated using Fluorescence-activated Cell Sorting (FACS) at 4 weeks and 8 weeks after tamoxifen induction, respectevely. Three old (20 months) and three young (3 months) mice (Pdzk1ip1-CreER R26Tom/Tom) were used for each timepoint.
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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 |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Apr 05, 2023 |
| Last update date |
Apr 28, 2023 |
| Contact name |
Stephania Contreras Castillo |
| Organization name |
Université de Bordeaux
|
| Street address |
2, Docteur Hoffman Martinot
|
| 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 (6)
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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 |
PRJNA952566 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229017_README_barcode_sequences_for_ADTs_HTOs.csv |
728 b |
(ftp)(http) |
CSV |
| GSE229017_wk4_barcodes.tsv.gz |
64.2 Kb |
(ftp)(http) |
TSV |
| GSE229017_wk4_features.tsv.gz |
284.4 Kb |
(ftp)(http) |
TSV |
| GSE229017_wk4_matrix.mtx.gz |
181.6 Mb |
(ftp)(http) |
MTX |
| GSE229017_wk4_raw_barcodes.tsv.gz |
10.5 Mb |
(ftp)(http) |
TSV |
| GSE229017_wk4_raw_features.tsv.gz |
254.4 Kb |
(ftp)(http) |
TSV |
| GSE229017_wk4_raw_matrix.mtx.gz |
342.6 Mb |
(ftp)(http) |
MTX |
| GSE229017_wk8_barcodes.tsv.gz |
54.1 Kb |
(ftp)(http) |
TSV |
| GSE229017_wk8_features.tsv.gz |
284.4 Kb |
(ftp)(http) |
TSV |
| GSE229017_wk8_matrix.mtx.gz |
122.8 Mb |
(ftp)(http) |
MTX |
| GSE229017_wk8_raw_barcodes.tsv.gz |
8.2 Mb |
(ftp)(http) |
TSV |
| GSE229017_wk8_raw_features.tsv.gz |
254.4 Kb |
(ftp)(http) |
TSV |
| GSE229017_wk8_raw_matrix.mtx.gz |
221.9 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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