کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2133871 1087433 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The transcription factor Mxd4 controls the proliferation of the first blood precursors at the onset of hematopoietic development in vitro
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The transcription factor Mxd4 controls the proliferation of the first blood precursors at the onset of hematopoietic development in vitro
چکیده انگلیسی

ObjectiveThe balance between proliferation and differentiation during hematopoietic development in the embryo is a complex process, the detailed molecular mechanisms of which remain to be fully characterized. The transcription factor Mxd4, a member of the Myc-Max-Mad network, was identified in a global gene expression profiling screen as being tightly regulated at the onset of hematopoietic lineage specification upon in vitro differentiation of mouse embryonic stem cells. Our study investigated the Mxd4 expression pattern at the onset of hematopoiesis and the biological relevance of its sharp and transient downregulation.Materials and MethodsTo study the expression pattern and role of Mxd4 at the onset of hematopoiesis, the in vitro differentiation of embryonic stem cells was used as a model system. Gain of function assays were performed using a doxycycline-inducible embryonic stem cell system.ResultsWe show here that Mxd4 expression is transiently downregulated at an early stage of commitment to the hematopoietic lineage. Enforced expression of Mxd4 at this period of differentiation results in a defect in hematopoietic progenitor development, with impaired development of both primitive and definitive blood lineages. This effect is due to a severe decrease in cell proliferation, with an increased frequency of cells in the G0/G1 phase of the cell cycle, alongside a reduced frequency of cells in the S phase.ConclusionsTogether our results indicate that during embryonic hematopoietic differentiation Mxd4 is an important player in the regulation of blood progenitor proliferation, and suggest that downregulation of its expression might be required for a proliferative burst preceding lineage specification.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 39, Issue 11, November 2011, Pages 1090–1100
نویسندگان
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