Integrin-α3 is a Functional Marker of <i>Ex Vivo</i> Expanded Long-Term Hematopoietic Stem Cells

UM171 Preserves Epigenetic Marks that Are Reduced in Ex Vivo Culture of Human HSCs via Potentiation of the CLR3-KBTBD4 Complex

“…UM171 was shown to rapidly upregulate the expression of EPCR on human HSCs whose robust and multilineage in vivo activity is restricted to EPCR positivity. Based on these results, EPCR has become a reliable marker for ex vivo expanded cord blood HSCs (Fares et al, 2017;Papa et al, 2018;Subramaniam et al, 2020;Tomellini et al, 2019). We also showed that EPCR's anti-inflammatory property is essential for UM171-induced HSC expansion (Chagraoui et al, 2019).…”

“…Again, the two deletion mutants appeared inactive (Figures 3B, 3C, and S3A). Our previous results showed that the in vivo repopulating activity of UM171-expanded cord blood cultures is in the CD34 + CD201 + fraction (Fares et al, 2017;Tomellini et al, 2019). Analysis of absolute CD34 + CD201 + cell counts in cultures engineered to overexpress KBTBD4 and treated with different doses of UM171 show indeed that more CD34 + CD201 + cells are produced under conditions of KBTBD4 overexpression, both in 5 nM and 35 nM UM171 (Figure 3C), although total cell counts are unchanged (Figure S3A, bottom left panel).…”

“…We also showed that EPCR's anti-inflammatory property is essential for UM171-induced HSC expansion (Chagraoui et al, 2019). Using UM171 as a tool compound, it was recently possible to show that human cord blood long-term (LT) HSCs co-express ITGA3 and EPCR, whereas those with more short-term (ST) potential express EPCR but lack ITGA3 (Tomellini et al, 2019).…”