Sequential development of hematopoietic and cardiac mesoderm during embryonic stem cell differentiation

  1. Valerie Kouskoff*,,
  2. Georges Lacaud*,,
  3. Staci Schwantz*,
  4. Hans Jöerg Fehling, and
  5. Gordon Keller*,§
  1. *Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029; and Department of Immunology, Medical Faculty/University Clinics, D-89070 Ulm, Germany
  1. Edited by Stuart H. Orkin, Harvard Medical School, Boston, MA, and approved July 13, 2005 (received for review March 1, 2005)

Abstract

The ability to generate a wide spectrum of differentiated cell types from ES cells in culture offers a powerful approach for studying lineage induction and specification and a promising source of progenitors for cell replacement therapy. Although significant efforts are being made to optimize culture conditions for the generation of different cell populations from ES cells, the identification and efficient isolation of specific progenitors for many lineages within these cultures remains a major challenge. By specifically tracking hematopoietic and cardiac development, we demonstrate here that these two lineages arise from distinct mesoderm subpopulations that develop in sequential waves from pre-mesoderm cells. Access to these populations provides a unique approach to isolate and characterize the earliest progenitors of these lineages.

Footnotes

  • § To whom correspondence should be addressed at: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029. E-mail: gordon.keller{at}mssm.edu.

  • Present address: Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.

  • Author contributions: V.K., G.L., and G.K. designed research; V.K., G.L., and S.S. performed research; H.J.F. contributed new reagents/analytic tools; V.K. and G.L. analyzed data; and V.K. and G.K. wrote the paper.

  • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviations: EB, embryoid body; BL-CFC, blast colony-forming cell; Bry, brachyury.

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