Because of the scarcity of megakaryocytes in hematopoietic tissues, studying megakaryopoiesis heavily relies on the availability of appropriate cellular models. Here, we report the establishment of a new mouse embryonic stem (ES) cell-derived megakaryocytic cell line, MKD1. The cells are factor-dependent, their cell surface immunophenotype and gene expression profile closely resemble that of primary megakaryocyte progenitors (MkPs) and they further differentiate along the megakaryocyte lineage upon valproic acid treatment. At a functional level, we show that ablation of SCL expression, a transcription factor critical for MkP maturation, leads to gene expression alterations similar to that observed in primary, Scl-excised MkPs. Moreover, the cell line is amenable to biochemical and transcriptional analyses, as we report for GpVI, a direct target of SCL. Thus, the MKD1 cell line offers a pertinent experimental model to study the cellular and molecular mechanisms underlying MkP biology and more broadly megakaryopoiesis.
Journal article
PLoS One
2012
7
Animals, Cell Culture Techniques, Cell Differentiation, Cell Line, Cell Lineage, Cells, Cultured, Embryonic Stem Cells, Gene Expression Profiling, Hematopoietic Stem Cells, Immunophenotyping, Megakaryocyte Progenitor Cells, Megakaryocytes, Mice, Mice, Transgenic, Promoter Regions, Genetic, Stem Cells, Transcription Factors, Transcription, Genetic