Embryonic stem (ES) cells differentiate into multiple hematopoietic lineages during embryoid body formation in vitro, but to date, an ES-derived hematopoietic stem cell has not been identified and subjected to clonal analysis in a manner comparable with hematopoietic stem cells from adult bone marrow. As the chronic myeloid leukemia-associated BCR/ABL oncogene endows the adult hematopoietic stem cell with clonal dominance without inhibiting pluripotent lymphoid and myeloid differentiation, we have used BCR/ABL as a tool to enable engraftment and clonal analysis. We show that embryoid body-derived hematopoietic progenitors expressing BCR/ABL maintain a primitive hematopoietic blast stage of differentiation and generate only primitive erythroid cell types in vitro. These cells can be cloned, and when injected into irradiated adult mice, they differentiate into multiple myeloid cell types as well as T and B lymphocytes. While the injected cells express embryonic (β-H1) globin, donor-derived erythroid cells in the recipient express only adult (β-major) globin, suggesting that these cells undergo globin gene switching and developmental maturation in vivo. These data demonstrate that an embryonic hematopoietic stem cell arises in vitro during ES cell differentiation that constitutes a common progenitor for embryonic erythroid and definitive lymphoid-myeloid hematopoiesis.
History of our journals
As our publisher, The Company of Biologists, turns 100 years old, read about Development’s journey and highlights from some its first issues, and explore the history of each of our sister journals: Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology
In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
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