Table 2.
Summary of human studies describing the effects of different inflammatory sources and pathways on phenotypically defined HSC
SourceInflammatory pathwayEffect on HSCsHSC phenotypeReference
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 LinCD34+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 LinCD133+CD45+ and CD34+CD38 Skirecki et al. (2019)  
 ND Minor increase mobilization at days 4 and 7 after septic shock Circulating CD34+CD38CD90+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 LinCD34+CD38 Weisser et al. (2016)  
CGD patients  Exhausted after in vitro culture G-CSF–mobilized CD34+CD38CD90+  
 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 LinCD34+CD38CD90+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 LinCD34+CD123low/−CD90+CD45RA Rundberg Nilsson et al. (2016)  
 ND Reduced in vitro plating efficiency and colony size   
  Intrinsic megakaryocytic/ erythroid bias (transcriptomics)   
SourceInflammatory pathwayEffect on HSCsHSC phenotypeReference
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 LinCD34+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 LinCD133+CD45+ and CD34+CD38 Skirecki et al. (2019)  
 ND Minor increase mobilization at days 4 and 7 after septic shock Circulating CD34+CD38CD90+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 LinCD34+CD38 Weisser et al. (2016)  
CGD patients  Exhausted after in vitro culture G-CSF–mobilized CD34+CD38CD90+  
 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 LinCD34+CD38CD90+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 LinCD34+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.

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