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  • Induced HSCs were derived from both

    2018-10-20

    Induced HSCs were derived from both mouse and human PSCs via intra-teratoma hematopoiesis, which provides a new tool for investigating the extrinsic and intrinsic factors of hematopoietic development (Amabile et al., 2013; Suzuki et al., 2013). We used this approach to confirm that OP9-Lhx2 promotes the production of both mouse and human hematopoietic progenitors in vivo. The derived hematopoietic progenitors engrafted and reconstituted myeloid and B lymphoid lineages in recipients, but they lacked the potential for T lymphopoiesis. We tested multiple ESC and iPSC lines and excluded the possibility that the defect in the T potential was due to defects in the individual PSC line. Hematopoietic progenitors derived from PSCs have been reported to possess a homing defect. This possibility was excluded in our experiment because engraftments via the intra-medullary tibia injection of teratoma-derived hematopoietic progenitors failed. Hematopoietic progenitors were also detected in the bone marrow of teratoma-bearing mice, but the transplantation of these substance p Supplier into myeloablated mice again failed to show engraftments. Thus, the hematopoietic progenitors derived from teratoma hematopoiesis in our experiment possessed intrinsic defects and could not self-renew in the long term. In our experimental settings, even the hematopoietic progenitors from individual teratomas showed transient engraftment only in a low ratio of the recipients, which indicated functional variations of hematopoetic cells derived from teratoma hematopoiesis. We detected human blood cells from bulk teratoma cells using FACS analysis and PCR of CFU cells, however, blood cells surrounded by bone-marrow-like niche in teratomas in our experiments are extremely rare, and the identity of human blood cells origin must be further evaluated by situ staining using human CD45 antibodies. In fact, the very limited 0.1%–2% hematopoietic chimerism in the bone marrow with predominant myeloid engraftment in as few as 4% recipients demonstrated that the teratoma hematopoiesis tool must be optimized further (Slukvin, 2013; Amabile et al., 2013; Suzuki et al., 2013). In conclusion, OP9-Lhx2 cells provide a better niche for the production of hematopoietic progenitors from PSCs, partially via the upregulation of Apln. OP9-Lhx2 might be used as a new tool for hematopoietic derivation both in vitro and in vivo. Our strategy might also be used to build additional niche cell lines by screening additional transcription factors that play important roles in hematopoietic development in a cell non-autonomous manner.
    Introduction White adipose tissue (WAT) is a major energy storage depot and endocrine gland (Gesta et al., 2007). Its physiological functions are mainly fulfilled by adipocytes arising out of adipose-derived stromal/progenitor cells (ASCs) (Yamamoto et al., 2007; Rodeheffer et al., 2008; Tang et al., 2008), which constitute a large pool of adipocyte precursors crucial for adipose tissue homeostasis and expansion (Hausman et al., 2001; Berry et al., 2013). Former studies implicating a predetermined number of fat cells at birth were refuted. In fact, in adult humans ~10% of all fat cells turnover each year (Spalding et al., 2008) and estimates indicate that young adult mice generate ~15% of adipocytes each month (Rigamonti et al., 2011). Different WAT depots, at subcutaneous (sWAT) and visceral (vWAT) sites, comprise distinct adipocyte populations, which are generated by several processes during and after development. These fat cell populations could arise from multiple germ layers and different progenitor cell types (Majka et al., 2011). In fact, it was shown that ASCs reside at the vascular interface and resemble mural cells that can proliferate and differentiate into adipocytes (Tang et al., substance p Supplier 2008). Moreover, although controversially discussed, studies suggest that endothelial cells and hematopoietic stem cells might give rise to a subset of adipocytes by changing fate into mural cells and then converting to progenitors (Crossno et al., 2006; Gupta et al., 2012; Medici et al., 2010; Sera et al., 2009; Tran et al., 2012).