Home LiteratureArticle Details
PMID: 17062726 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Blood ·Vol. 109 ·No. 4 ·2007-02-15 ·Pages 1433-41

Tober J, Koniski A, McGrath KE, Vemishetti R, Emerson R, de Mesy-Bentley KK, Waugh R, Palis J

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.

MeSH Terms
Animals Blood Platelets/cytology Cell Lineage/physiology Erythroid Precursor Cells/cytology Gastrula/cytology Hematopoiesis Hematopoietic Stem Cells/cytology Megakaryocytes/cytology Mice Mice, Inbred ICR Multipotent Stem Cells/cytology Yolk Sac/blood supply
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Tober Joanna
Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester Medical Center, NY 14642, USA.
Koniski Anne
McGrath Kathleen E
Vemishetti Radhika
Emerson Rachael
de Mesy-Bentley Karen K L
Waugh Richard
Palis James
References (71)
71 references, click to expand
  1. Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes.
    Blood. 1998 Sep 1;92(5):1608-16 PMID: 9716588
  2. In vitro release of vascular endothelial growth factor during platelet aggregation.
    Am J Physiol. 1998 Sep;275(3 Pt 2):H1054-61 PMID: 9724313
  3. Whole blood analysis of reticulated platelets: improvements of detection and assay stability.
    Cytometry. 1998 Oct 15;34(5):229-34 PMID: 9822309
  4. Evidence that platelets promote tube formation by endothelial cells on matrigel.
    Br J Pharmacol. 1998 Nov;125(6):1252-7 PMID: 9863654
  5. GATA1 mutations in Down syndrome: implications for biology and diagnosis of children with transient myeloproliferative disorder and acute megakaryoblastic leukemia.
    Pediatr Blood Cancer. 2005 Jan;44(1):40-4 PMID: 15390312
  6. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo.
    Nature. 2004 Dec 2;432(7017):625-30 PMID: 15577911
  7. Interplay of pu.1 and gata1 determines myelo-erythroid progenitor cell fate in zebrafish.
    Dev Cell. 2005 Jan;8(1):97-108 PMID: 15621533
  8. The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP).
    Blood. 1975 Apr;45(4):551-62 PMID: 1167796
  9. Role of stem cell migration in initiation of mouse foetal liver haemopoiesis.
    Nature. 1975 Dec 25;258(5537):726-8 PMID: 1207754
  10. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse.
    Development. 1999 Nov;126(22):5073-84 PMID: 10529424
  11. Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2.
    Blood. 1999 Nov 1;94(9):3037-47 PMID: 10556187
  12. Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes.
    J Cell Biol. 1999 Dec 13;147(6):1299-312 PMID: 10601342
  13. Structural and functional characterization of the mouse von Willebrand factor receptor GPIb-IX with novel monoclonal antibodies.
    Blood. 2000 Feb 1;95(3):886-93 PMID: 10648400
  14. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages.
    Nature. 2000 Mar 9;404(6774):193-7 PMID: 10724173
  15. Identification and characterization of a bipotent (erythroid and megakaryocytic) cell precursor from the spleen of phenylhydrazine-treated mice.
    Blood. 2000 Apr 15;95(8):2559-68 PMID: 10753835
  16. Platelet-released phospholipids link haemostasis and angiogenesis.
    Cardiovasc Res. 2001 Feb 16;49(3):588-99 PMID: 11166272
  17. Evidence for the presence of murine primitive megakaryocytopoiesis in the early yolk sac.
    Blood. 2001 Apr 1;97(7):2016-22 PMID: 11264166
  18. Regulation of hemangioblast development.
    Ann N Y Acad Sci. 2001 Jun;938:96-107; discussion 108 PMID: 11458531
  19. Fetal liver myelopoiesis occurs through distinct, prospectively isolatable progenitor subsets.
    Blood. 2001 Aug 1;98(3):627-35 PMID: 11468160
  20. Yolk-sac hematopoiesis: the first blood cells of mouse and man.
    Exp Hematol. 2001 Aug;29(8):927-36 PMID: 11495698
  21. Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1.
    Nat Genet. 2005 Jun;37(6):613-9 PMID: 15895080
  22. Hematopoiesis in the yolk sac: more than meets the eye.
    Exp Hematol. 2005 Sep;33(9):1021-8 PMID: 16140150
  23. Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1.
    Blood. 2006 Jan 1;107(1):87-97 PMID: 16144799
  24. "Maturational" globin switching in primary primitive erythroid cells.
    Blood. 2006 Feb 15;107(4):1665-72 PMID: 16263786
  25. A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481.
    Blood. 2006 Jun 15;107(12):4606-13 PMID: 16469874
  26. GATA1 in normal and malignant hematopoiesis.
    Semin Cell Dev Biol. 2005 Feb;16(1):137-47 PMID: 15659348
  27. The homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo.
    Dev Biol. 2005 Apr 15;280(2):307-20 PMID: 15882575
  28. Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro.
    Blood. 2002 Jul 15;100(2):458-66 PMID: 12091336
  29. Prospective isolation of human clonogenic common myeloid progenitors.
    Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11872-7 PMID: 12193648
  30. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver.
    Development. 2002 Nov;129(21):4891-9 PMID: 12397098
  31. Characterization of mouse clonogenic megakaryocyte progenitors.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):205-10 PMID: 12490656
  32. Thrombopoietin promotes mixed lineage and megakaryocytic colony-forming cell growth but inhibits primitive and definitive erythropoiesis in cells isolated from early murine yolk sacs.
    Blood. 2003 Feb 15;101(4):1329-35 PMID: 12393382
  33. Circulation is established in a stepwise pattern in the mammalian embryo.
    Blood. 2003 Mar 1;101(5):1669-76 PMID: 12406884
  34. A role for thrombopoietin in hemangioblast development.
    Stem Cells. 2003;21(3):272-80 PMID: 12743322
  35. The birth of the platelet.
    J Thromb Haemost. 2003 Jul;1(7):1580-6 PMID: 12871294
  36. Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation.
    Development. 2003 Sep;130(17):4217-27 PMID: 12874139
  37. CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo.
    Development. 2003 Sep;130(18):4393-403 PMID: 12900455
  38. Characterization of Notch3-deficient mice: normal embryonic development and absence of genetic interactions with a Notch1 mutation.
    Genesis. 2003 Nov;37(3):139-43 PMID: 14595837
  39. Production of functional platelets by differentiated embryonic stem (ES) cells in vitro.
    Blood. 2003 Dec 1;102(12):4044-51 PMID: 12920021
  40. Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome.
    Blood. 2004 Jan 15;103(2):399-406 PMID: 14512321
  41. Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis.
    Blood. 2004 Jul 1;104(1):19-25 PMID: 15031208
  42. Analysis of hematopoietic progenitors in the mouse embryo.
    Methods Mol Med. 2005;105:289-302 PMID: 15492402
  43. Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo.
    Br J Haematol. 1970 Mar;18(3):279-96 PMID: 5491581
  44. Cholinesterase as a possible marker for early cells of the megakaryocytic series.
    Blood. 1973 Sep;42(3):413-21 PMID: 4125240
  45. Transcriptional regulation of erythropoiesis: an affair involving multiple partners.
    Oncogene. 2002 May 13;21(21):3368-76 PMID: 12032775
  46. Induction of megakaryocyte colonies with platelet formation in vitro.
    Nature. 1976 Jun 10;261(5560):492-4 PMID: 934282
  47. Human platelet size, shape, and related functions in health and disease.
    Physiol Rev. 1982 Jan;62(1):185-261 PMID: 7034009
  48. Single-cell origin of mouse hemopoietic colonies expressing multiple lineages in variable combinations.
    Proc Natl Acad Sci U S A. 1983 Nov;80(21):6689-93 PMID: 6579554
  49. Properties of the earliest clonogenic hemopoietic precursors to appear in the developing murine yolk sac.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):3851-4 PMID: 3012535
  50. The ultrastructure of megakaryopoietic cells of the yolk sac and liver in mouse embryo.
    Anat Rec. 1988 Oct;222(2):164-9 PMID: 3213966
  51. Flow cytometric analysis of thiazole orange uptake by platelets: a diagnostic aid in the evaluation of thrombocytopenic disorders.
    Blood. 1990 Jan 1;75(1):116-21 PMID: 1688494
  52. Megakaryocytes in the yolk sac, liver and bone marrow of the mouse: a cytometrical analysis by semithin light microscopy.
    J Anat. 1989 Dec;167:181-7 PMID: 2630532
  53. Development of hematopoietic stem cell activity in the mouse embryo.
    Immunity. 1994 Jul;1(4):291-301 PMID: 7889417
  54. Demonstration that thiazole-orange-positive platelets in the dog are less than 24 hours old.
    Blood. 1995 Apr 1;85(7):1822-5 PMID: 7535589
  55. Suppression of erythro-megakaryocytopoiesis and the induction of reversible thrombocytopenia in mice transgenic for the thymidine kinase gene targeted by the platelet glycoprotein alpha IIb promoter.
    J Exp Med. 1995 Jun 1;181(6):2141-51 PMID: 7760003
  56. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development.
    Cell. 1995 Jun 2;81(5):695-704 PMID: 7774011
  57. In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation.
    Exp Hematol. 1995 Aug;23(9):996-1001 PMID: 7635185
  58. Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy.
    J Clin Invest. 1995 Sep;96(3):1683-7 PMID: 7657840
  59. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis.
    Cell. 1996 Jan 26;84(2):321-30 PMID: 8565077
  60. Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin.
    J Exp Med. 1996 Feb 1;183(2):651-6 PMID: 8627177
  61. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl.
    Blood. 1996 Mar 15;87(6):2162-70 PMID: 8630375
  62. Characterization of a bipotent erythro-megakaryocytic progenitor in human bone marrow.
    Blood. 1996 Aug 15;88(4):1284-96 PMID: 8695846
  63. Reticulated platelet values in normal and thrombocytopenic neonates.
    J Pediatr. 1996 Aug;129(2):269-74 PMID: 8765626
  64. Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor.
    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9126-31 PMID: 8799165
  65. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets.
    Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):663-8 PMID: 9012841
  66. A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development.
    EMBO J. 1997 Jul 1;16(13):3965-73 PMID: 9233806
  67. Flow cytometric analysis of reticulated platelets: evidence for a large proportion of non-specific labelling of dense granules by fluorescent dyes.
    Br J Haematol. 1998 Feb;100(2):351-7 PMID: 9488626
  68. A common precursor for hematopoietic and endothelial cells.
    Development. 1998 Feb;125(4):725-32 PMID: 9435292
  69. Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages.
    Development. 1998 May;125(9):1747-57 PMID: 9521912
  70. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG.
    Genes Dev. 1998 Apr 15;12(8):1176-88 PMID: 9553047
  71. Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors.
    Blood. 1998 May 1;91(9):3134-43 PMID: 9558367
Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-06-031898
Published
2007-02-15
Epub
2006-00-24
Pages
1433-41
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1794060
Subset
IM
External Links
PubMed source DOI: 10.1182/blood-2006-06-031898 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2