Table 1.
Studies that identified angptl2 as a member of the SASP.
| Cell/Tissue | Species (Model Used) |
Treatment/Senescence Inducer | Changes in Angptl2 Gene Expression | Fold Change | Methods | GEO Number |
Reference | |
|---|---|---|---|---|---|---|---|---|
| Fibroblasts | Primary fibroblast cell lines (WS1, WI-38 & BJ) | Homo Sapiens (in vitro) |
Replicative senescence (serial passages) |
↓ in senescent and quiescent fibroblasts | −0.86 range (−2.84; 1.13) |
cDNA microarray | NA | [58] |
| Primary fibroblast cell line (IMR90) | Homo Sapiens (in vitro) |
Oncogene-induced senescence (100 nM 4-hydroxytamoxifen treatment for 0–7 days) | ↓ in senescent fibroblasts | −1.63 | cDNA microarray | GSE41318 | [63] | |
| Embryonic fibroblast cell line (MRC-5) | Homo Sapiens (in vitro) |
SCM-induced senescence (time course over 5 days) |
↓ at three time points: day 1, day 3 & day 5 vs. day 0 |
D1 vs. D0 = −2.39 D3 vs. D0 = −1.93 D5 vs. D0 = −2.49 |
RNA-seq | NA | [64] | |
| Primary fibroblast cell line (IMR-90) | Homo Sapiens (in vitro) |
Replicative senescence (exhaustion PDL 50–59) IR-induced senescence (PDL 25 exposed to 10 Gy) |
↓ in senescent fibroblasts | RS = −1.59 IR = −1.28 |
RNA-seq | GSE130727 | [65] | |
| Fibroblasts from healthy skin samples | Homo Sapiens (in vivo) |
Aging (young (25–27 years) and old subjects (53–70 years) |
↓ in mesenchymal fibroblasts | −1.31 | single-cell RNA-seq | GSE130973 | [66] | |
| Fibroblasts from Werner Syndrome patients Premature aging disorder | Homo Sapiens (in vivo) |
Patients# A0031: 37 years old TIG-114: 36 years old WSCU01: 63 years old |
↑ in WS fibroblasts (vs. healthy fibroblasts) | A0031 = +10.4 TIG-114 = +5.9 WSCU01 = +7.3 |
cDNA microarray | NA | [67] | |
| Primary fibroblast cell lines (HFF) | Homo Sapiens (in vitro) |
Replicative senescence (serial passages up to PDL 74) |
↑ in HFF senescent fibroblasts | PDL 16–26 = +1.38 PDL 16–74 = +2.68 |
RNA-seq | GSE63577 | [68] | |
| Primary fibroblast cell lines (MRC-5, WI-38, BJ, IMR-90 & HFF) | Homo Sapiens (in vitro) |
Replicative senescence (serial passages up to PDL 74) |
↑ in WI-38 senescent fibroblasts (vs. early PDL) | ND angptl2 is the 63rd most up-regulated gene |
RNA-seq | GSE63577 | [69] | |
| Primary fibroblast cell line (WI-38) | Homo Sapiens (in vitro) |
IR-induced senescence (PDL 25 exposed to 10 Gy) |
↑ in WI-38 senescent fibroblasts | +1.15 | RNA-seq | GSE130727 | [65] | |
| Primary fibroblast cell line (IMR-90) | Homo Sapiens (in vitro) |
Paracrine- and oncogene-induced senescence (4-hydroxytamoxifen treatment) | ↑ in senescent fibroblasts | ND | single-cell RNA-seq | GSE115301 | [70] | |
| Hepatocytes | Hepatocellular carcinoma cell line (Huh7 clones) | Homo Sapiens (in vitro) |
Reprogramming replicative senescence (clone C3: PDL80; clone G12: PDL 90) |
↓ in senescent Huh7 clones C3 and G12 | ND | cDNA microarray | GSE17546 | [71] |
| Hepatocellular carcinoma cell line (HepG2) | Homo Sapiens (in vitro) |
Oncogene-induced senescence (10 µM and 100 µM etoposide treatment for 30 h) | ↑ in hepatocytes exposed to etoposide | 10 µM vs. ctrl = +3.63 100 µM vs. ctrl = +1.76 10 µM vs. 100 µM = +2.06 |
cDNA microarray | GSE61110 | [72] | |
| Hepatocellular carcinoma cells from patients | Homo Sapiens (in vivo) |
Oncogene-induced senescence (liver cancer) | ↑ between predicted high and low risk HCC cases | high vs. low risk = +1.16 | cDNA microarray | GSE14520 | [73] | |
| Astrocytes | Fetal astrocytes | Homo Sapiens (in vitro) |
Oxidative stress-induced senescence (200 µM H2O2 treatment for 2 h) | ↑ between pre-senescent and senescent astrocytes | pre vs. senescent = +2.05 | RNA-seq | GSE58910 | [74] |
| Primary astrocyte cell line | Homo Sapiens (in vitro) |
IR-induced senescence (exposed to 10 Gy) | ↑ between non-senescent and senescent astrocytes | +1.21 | RNA-seq | NA | [75] | |
| Vasculature | Aortic smooth muscle cells | Homo Sapiens (in vitro) |
Replicative senescence (serial passages growing population = PDL 14 senescent population = PDL 39–42) |
↓ in VSMC from late PDL vs. early PDL | −2.8 | cDNA microarray | NA | [76] |
| Endothelial cell lines (HUVEC & HAEC) | Homo Sapiens (in vitro) |
IR-induced senescence (exposed to 4 Gy) | ↓ in senescent ECs | HAECs = −0.21 | RNA-seq | GSE130727 | [65] | |
| Pericytes from brain of young and old mice (C57Bl/6) | Mus Musculus (in vivo) |
Aging (young mice: 3 months old aged mice: 28 months old) |
↓ in pericytes from young to old mice brain | ND % expression: 20% (young) vs. 10% (aged) |
single-cell RNA-seq | NA | [77] | |
| Arterial endothelial cells from aortic artery | Macaca Fascicularis (in vivo) |
Replicative senescence (young monkey: 4–6 years old old monkey: 18–21 years old) |
↓ in senescent aortic ECs | −0.38 | single-cell RNA-seq | GSE117715 | [78] | |
| Endothelial cells derived from embryonic stem cells | Homo Sapiens (in vitro) |
Replicative senescence (serial passages in FOXO3A−/− ECs) | ↓ in senescent FOXO3A−/− ECs | −0.87 | single-cell RNA-seq | GSE117715 | [78] | |
| Others | Prostate and uterus (healthy samples) | Homo Sapiens (in vivo) |
Aging (1-year follow-up in healthy individuals 20–79 years old) | ↓ in healthy tissues upon aging (1 year) | Prostate = −0.01 Uterus = −0.02 |
RNA-seq | NA | [79] |
| Breast and uterus tumor samples | Homo Sapiens (in vivo) |
Aging (1-year follow-up in breast and uterus cancer patients) | ↓ in cancerous tissues upon aging (1 year) | Breast = −1.94 Uterus = −1.77 |
RNA-seq | NA | [79] | |
| Platelets from healthy donors | Homo Sapiens (in vitro) |
Replicative senescence (healthy platelets stored under standard blood banking conditions for 5 days) | ↑ between day 0 and day 5 | +3.00 | microarray | NA | [80] | |
| Brain tumor samples | Homo Sapiens (in vivo) |
Aging (1-year follow-up in brain cancer patients) | ↑ in cancerous tissue upon aging (1 year) | +1.75 | RNA-seq | NA | [79] |
GEO: gene expression omnibus accession number; IR: ionizing radiation; NA: non applicable; ND: not determined; PDL: population doubling length; SCM: stem cell medium (ROS-induced oxidation). ↑: up-regulation; ↓: down-regulation.