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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-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

An epithelial‐mesenchymal transition (EMT) is a critical process during embryonic development and the progression of epithelial tumors to metastatic cancers. Gene expression profiling has uncovered the transcription factor LIM homeobox gene 2 (Lhx2) with up‐regulated expression during TGFβ‐induced EMT in normal and cancerous breast epithelial cells. Loss and gain of function experiments in transgenic mouse models of breast cancer and of insulinoma in vivo and in breast cancer cells in vitro indicate that Lhx2 plays a critical role in primary tumor growth and metastasis. Notably, the transgenic expression of Lhx2 during breast carcinogenesis promotes vessel maturation, primary tumor growth, tumor cell intravasation and metastasis by directly inducing the expression of platelet‐derived growth factor (PDGF)‐B in tumor cells and by indirectly increasing the expression of PDGF receptor‐β (PDGFRβ) on tumor cells and pericytes. Pharmacological inhibition of PDGF‐B/PDGFRβ signaling reduces vessel functionality and tumor growth and Lhx2‐induced cell migration and cell invasion. The data indicate a dual role of Lhx2 during EMT and tumor progression: by inducing the expression of PDGF‐B, Lhx2 provokes an autocrine PDGF‐B/PDGFRβ loop required for cell migration, invasion and metastatic dissemination and paracrine PDGF‐B/PDGFRβ signaling to support blood vessel functionality and, thus, primary tumor growth. Highlights: Lhx2 expression is induced during EMT by canonical TGFβ signaling.Lhx2 expression is elevated during both human and mouse carcinogenesis.Lhx2 promotes primary tumor growth by paracrine PDGF‐B/PDGFRβ signaling‐mediated tumor vessel maturation and functionality.Lhx2 promotes metastasis formation via autocrine PDGF‐B/PDGFRβ signaling‐induced tumor cell migration and invasion. [ABSTRACT FROM AUTHOR]