OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

Stem Cell Research
Xiaoli ChenJinyong Wang

Abstract

Generating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lh...Continue Reading

References

Feb 12, 2010·Cold Spring Harbor Protocols·Roxanne Holmes, Juan Carlos Zúñiga-Pflücker
May 23, 2012·Blood·Qing C YuAndrew G Elefanty
May 15, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Nao SuzukiHiromitsu Nakauchi

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Citations

Mar 22, 2018·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Haide ChenHe Huang

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