Table 2 Recent single-cell studies on HSC aging at the genetic and epigenetic levels
From: Mechanisms and rejuvenation strategies for aged hematopoietic stem cells
Author and year | Age of object Number of analyzed cells /measured cells Cell types | Methods | Conclusion |
|---|---|---|---|
Kowalczyk et al. 2015 [22] | Young mice: 2–3 months; 176/200 (each type) Aged mice: > 22 months; 176/200 (each type) LT-HSC: LSK CD150+CD48− ST-HSC: LSK CD150−CD48− MPP: LSK CD150−CD48+ | SMART-seq | Cell cycle-related genes dominated the transcriptome variability. There was a lower frequency of cells in the G1 phase among old long-term HSCs. |
Grover et al. 2016 [25] | Young mice: 2–3 months; 52/61 Aged mice: 20–25 months; 62/74 LSK CD150+CD48− | Fluidigm C1 single-cell AutoPrep system | The principal pathways enriched in young HSCs were involved in cell cycle progression, while those in old HSCs were involved in growth factor signaling. |
Mann et al. 2018 [34] | Young mice: 2–3 months; 124~186 (each type) Aged mice: 20–24 months; 124~186 (each type) LT-HSC: LSKCD150+CD48− ST-HSC: LSK CD150−CD48− MPP: LSK CD150−CD48+ | SMART-Seq2 | LT-HSCs from young and aged mice had differential responses to inflammatory challenge. CD61 was a marker of myeloid-biased LT-HSCs. |
Frisch et al. 2019 [11] | Young mice: 1.5–2 months Aged mice: 20–24 months LSK CD150+CD48−Flt3− | Fluidigm C1 single-cell AutoPrep system | Most aged LT-HSCs highly expressed megakaryocyte-biased genes, including Selp, Vwf, and Itgb3. CD41 and CD61 were associated with aged megakaryocytic HSC bias. |
Oetjen et al. 2018 [118] | Humans across an age range from 24~84 years 76,645/> 90,000 Mononuclear cells in BM | 10X genomics single-cell 3′ solution | The authors identified all the major BM mononuclear populations and age-associated changes in cell population frequencies. |
Hennrich et al. 2018 [114] | Young humans: < 30 years; 291 Aged humans: > 50 years; 228 CD34+ | SMART-seq2 | The mRNA levels of age-increased glycolytic enzymes were higher in myeloid-primed than in lymphoid-primed HSPCs. |
Adelman et al. 2019 [15] | Young humans: < 40 years; 338 Aged humans: > 60 years; 310 Lin-CD34+CD38− | Fluidigm C1 single-cell AutoPrep system | The authors observed a decrease in cycling-HSC and lymphoid-primed multipotent progenitors with age. |
Florian et al. 2018 [119] | Young mice: 2.5–3 months Aged mice: 20–26 months LSK CD34−Flk2− | scATAC-seq | Young HSCs divided mainly asymmetrically, while aged HSCs divided primarily symmetrically. |
Cheung et al. 2018 [85] | Young humans: < 25 years Aged humans: > 65 years Primary human immune cells | Epigenetic landscape profiling using cytometry by time-of-flight (EpiTOF) | The authors found consistent increases in chromatin marks in a broad array of cell subtypes from hematopoietic progenitors to terminally differentiated immune cells. |