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The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis.

ABSTRACT: In the adult, platelets are derived from unipotential megakaryocyte colony-forming cells (Meg-CFCs) that arise from bipotential megakaryocyte/erythroid progenitors (MEPs). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes, and circulating platelets, were examined in the murine embryo. We found that a majority of hemangioblast precursors during early gastrulation contains megakaryocyte potential. Combining progenitor assays with immunohistochemical analysis, we identified 2 waves of MEPs in the yolk sac associated with the primitive and definitive erythroid lineages. Primitive MEPs emerge at E7.25 along with megakaryocyte and primitive erythroid progenitors, indicating that primitive hematopoiesis is bilineage in nature. Subsequently, definitive MEPs expand in the yolk sac with Meg-CFCs and definitive erythroid progenitors. The first GP1bbeta-positive cells in the conceptus were identified in the yolk sac at E9.5, while large, highly reticulated platelets were detected in the embryonic bloodstream beginning at E10.5. At this time, the number of megakaryocyte progenitors begins to decline in the yolk sac and expand in the fetal liver. We conclude that the megakaryocyte lineage initially originates from hemangioblast precursors during early gastrulation and is closely associated both with primitive and with definitive erythroid lineages in the yolk sac prior to the transition of hematopoiesis to intraembryonic sites.

SUBMITTER: Tober J

PROVIDER: S-EPMC1794060 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis.

Tober Joanna J Koniski Anne A McGrath Kathleen E KE Vemishetti Radhika R Emerson Rachael R de Mesy-Bentley Karen K L KK Waugh Richard R Palis James J

Blood 20061024 4

In the adult, platelets are derived from unipotential megakaryocyte colony-forming cells (Meg-CFCs) that arise from bipotential megakaryocyte/erythroid progenitors (MEPs). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes, and circulating platelets, were examined in the murine embryo. We found that a majority of hemangioblast precursors during early gastrulation contains megakaryocyte potent ...[more]

PMID: 17062726

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Project description:The transcription factors SCL/Tal-1 and AML1/Runx1 control the generation of pluripotent hematopoietic stem cells (pHSC) and, thereby, primitive and definitive hematopoiesis, during embryonic development of the mouse from mesoderm. Thus, Runx1-deficient mice generate primitive, but not definitive hematopoiesis, while Tal-1-deficient mice are completely defective. Primitive as well as definitive hematopoiesis can be developed "in vitro" from embryonic stem cells (ESC). We show that wild type, as well as Tal-1(-/-) and Runx1(-/-) ESCs, induced to differentiation, all expand within 5 days to comparable numbers of Flk1(+) mesodermal cells. While wild type ESCs further differentiate to primitive and definitive erythrocytes, to c-fms(+)Gr1(+)Mac1(+) myeloid cells, and to B220(+)CD19(+) B- and CD4(+)/CD8(+) T-lymphoid cells, Runx1(-/-) ESCs, as expected, only develop primitive erythrocytes, and Tal-1(-/-) ESCs do not generate any hematopoietic cells. Retroviral transduction with Runx1 of Runx1(-/-) ESCs, differentiated for 4 days to mesoderm, rescues definitive erythropoiesis, myelopoiesis and lymphopoiesis, though only with 1-10% of the efficiencies of wild type ESC hematopoiesis. Surprisingly, Tal-1(-/-) ESCs can also be rescued at comparably low efficiencies to primitive and definitive erythropoiesis, and to myelopoiesis and lymphopoiesis by retroviral transduction with Runx1. These results suggest that Tal-1 expression is needed to express Runx1 in mesoderm, and that ectopic expression of Runx1 in mesoderm is sufficient to induce primitive as well as definitive hematopoiesis in the absence of Tal-1. Retroviral transduction of "in vitro" differentiating Tal-1(-/-) and Runx1(-/-) ESCs should be a useful experimental tool to probe selected genes for activities in the generation of hematopoietic progenitors "in vitro", and to assess the potential transforming activities in hematopoiesis of mutant forms of Tal-1 and Runx1 from acute myeloid leukemia and related tumors.

Dataset Information

The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis.

Publications

The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis.

Similar Datasets

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