Table 2. Summary of human studies describing the effects of different inflammatory sources and pathways on phenotypically defined HSC.
| Source | Inflammatory pathway | Effect on HSCs | HSC phenotype | Reference |
|---|---|---|---|---|
| Viral | ||||
| HIV patients | Not direct infection | Decreased pool | CD34+CD38− | Marandin et al. (1996) |
| TNF-α–induced Fas | Apoptosis | CD34+ | Isgrò et al. (2004) | |
| IL-18 increase; stem cell factor decrease | Decreased pool | Circulating Lin−CD34+CD45RA+CD10+CD117− | Bordoni et al. (2018) | |
| HIV humanized mice | pDCs (via IFN-α/β?) | Decreased pool and colony formation | CD34+CD38− | Li et al. (2017) |
| Bacterial | ||||
| Sepsis patients | Increased CXCL12 and decrease S1P at day 1 after septic shock | Increased mobilization and proliferation at day 3 after septic shock | Circulating Lin−CD133+CD45+ and CD34+CD38− | Skirecki et al. (2019) |
| ND | Minor increase mobilization at days 4 and 7 after septic shock | Circulating CD34+CD38−CD90+CD45RA− | Wang et al. (2021) | |
| Sepsis humanized mice | Increased TLR4 and CXCR4 expression/notch–Jagged1 signaling | Increased pool and proliferation | CD34+CD38− | Skirecki et al. (2015) |
| Inflammatory disease | Increased proinflammatory milieu (IL-1β, according to mouse model) | Decreased pool | Lin−CD34+CD38− | Weisser et al. (2016) |
| CGD patients | Exhausted after in vitro culture | G-CSF–mobilized CD34+CD38−CD90+ | ||
| Increased TNF-α | Decreased pool and increased apoptosis | CD34+ | Papadaki et al. (2002) | |
| RA patients | ND/premature telomere shortening | Decreased pool | Circulating CD34+ | Colmegna et al. (2008) |
| Impaired proliferative potential | ||||
| Increased TNF-α | Decreased pool and colony formation | CD34+ | Porta et al. (2004) | |
| SLE patients | Increased Fas (via TNF-α?) | Decreased pool and colony formation | CD34+CD38− | Papadaki et al. (2001) |
| Enhanced CD40–CD40L | Decreased pool and increased apoptosis | CD34+ | Pyrovolaki et al. (2009) | |
| ND | Increased pool | CD34+CD38− | Taraldsrud et al. (2009) | |
| ND | Increased pool | CD34+CD38− | Kuranda et al. (2011) | |
| Decrease in myeloid lineage bias in vivo (NSG mice) and in vitro | ||||
| Increased ERK/MAPK and GM-CSF signaling (tanscriptomics) | Increased pool and reduced quiescence | Lin−CD34+CD38−CD90+CD45RA− | Pang et al. (2011) | |
| Aging | ||||
| Elderly individuals | Reduced in vitro plating efficiency and increased myeloid bias | |||
| Reduced in vivo (NSG mice) engraftment and increased myeloid bias | ||||
| ND | Increased pool | CD34+ | Woolthuis et al. (2014) | |
| Impaired reconstitution capacity at 1 yr after autologous stem cell transplantation | ||||
| Increased pool | Lin−CD34+CD123low/−CD90+CD45RA− | Rundberg Nilsson et al. (2016) | ||
| ND | Reduced in vitro plating efficiency and colony size | |||
| Intrinsic megakaryocytic/ erythroid bias (transcriptomics) |
pDC, plasmacytoid dendritic cells.