BMP4 regulation of human megakaryocytic differentiation is involved in thrombopoietin signaling

Abstract

Activin A, BMP2, and BMP4, 3 members of the transforming growth factor-␤ family, are involved in the regulation of hematopoiesis. Here, we explored the role of these molecules in human megakaryopoiesis using an in vitro serum-free assay. Our results highlight for the first time that, in the absence of thrombopoietin, BMP4 is able to induce CD34 ؉ progenitor differentiation into megakaryocytes through all stages. Although we have previously shown that activin A and BMP2 are involved in erythropoietic commitment, these molecules have no effect on human megakaryopoietic engagement and differentiation. Using signaling pathway-specific inhibitors, we show that BMP4, like thrombopoietin, exerts its effects on human megakaryopoiesis through the JAK/STAT and mTor path-

CpG-Oligodeoxynucleotide Inhibits Smad-Dependent Bone Morphogenetic Protein Signaling: Effects on Myeloma Cell Apoptosis and In Vitro Osteoblastogenesis

“…These adverse effects of CpG-ODN therapy include anemia, thrombocytopenia, and neutropenia (7). BMPs regulate hematopoiesis (43)(44)(45), including erythropoiesis and the differentiation of megacaryocytes (46,47). The hematological side effects from CpG-ODN treatment can thus be due to TLR9-dependent activation of the immune system, or possibly also due to TLR9-independent side effects such as interference with BMP signaling.…”

miR-99a/100∼125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling

“…S7G-J). Activin A reduced the expansion of MPs during in vitro culture, while high levels of BMP4 slightly increased their proliferation (Maguer-Satta et al 2003;Jeanpierre et al 2008). Tricistron-transduced CD34 + HSPCs were resistant to both effects (Supplemental Fig.…”

Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation

“…9 After 5 days of culture, viable cells excluding trypan blue were numbered, and the relative proportions and maturation of erythrocytic and megakaryocytic cells were determined by fluorescence-activated cell sorting (FACS) after doublelabeling with labeled anti-CD71 and anti-Ter119, anti-CD61 and anti-CD41, or anti-CD41 and anti-CD42b antibodies. For single-cell progeny analyses, single MEPs were plated in 96-well plates using a FACSVantage flow cytometer coupled with single-cell depositor in 60 L of the same liquid medium with serum.…”

“…8 More recently, in vitro cultures have shown that TPO induces BMP4 production and autocrine stimulation of megakaryopoiesis initiated from human CD34 ϩ progenitors. 9 The specific combination of transcription factors allowing erythrocytic or megakaryocytic lineages commitment remains poorly understood. 10,11 Indeed, both lineages are dependent on many common transcription factors including Gata1, Tal1, Nfe2, Gfi1b, Zbp89, as well as cofactors like Fog1, Lmo2, or Ldb1 acting in large multiprotein complexes such as Fog1/Gata1/Zbp89 12 or Gata1/Tal1/Lmo2/Ldb1.…”