Long-Term Engraftment of ESC-Derived B-1 Progenitor Cells Supports HSC-Independent Lymphopoiesis

Yang Lin, Michihiro Kobayashi, Nathalia Azevedo Portilho, Akansha Mishra, Hongyu Gao, Yunlong Liu, Pamela Wenzel, Brian Davis, Mervin C. Yoder, Momoko Yoshimoto

Research output: Contribution to journalArticle

2 Scopus citations


It is generally considered that mouse embryonic stem cell (ESC) differentiation into blood cells in vitro recapitulates yolk sac (YS) hematopoiesis. As such, similar to YS-derived B-progenitors, we demonstrate here that ESC-derived B-progenitors differentiate into B-1 and marginal zone B cells, but not B-2 cells in immunodeficient mice after transplantation. ESC-derived B-1 cells were maintained in the recipients for more than 6 months, secreting natural IgM antibodies in vivo. Gene expression profiling displayed a close relationship between ESC- and YS-derived B-1 progenitors. Because there are no hematopoietic stem cells (HSCs) detectable in our ESC differentiation culture, successful long-term engraftment of ESC-derived functional B-1 cells supports the presence of HSC-independent B-1 cell development. Yoshimoto and colleagues demonstrate that mouse ESC-derived B-progenitors engraft in the immunodeficient mice long-term without gene manipulation as IgM-secreting B-1 and MZ B cells, but not conventional B-2 cells. These ESC-derived B-progenitors are molecularly similar to YS-derived B-progenitors. Since no HSCs are produced in their ESC differentiation system, this result supports the emerging paradigm-shifting concept of HSC-independent lymphopoiesis.

Original languageEnglish (US)
Pages (from-to)572-583
Number of pages12
JournalStem Cell Reports
Issue number3
StatePublished - Mar 5 2019


  • B-1 cells
  • ESCs
  • HSC-independent lymphopoiesis
  • mouse embryo
  • yolk sac

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Lin, Y., Kobayashi, M., Azevedo Portilho, N., Mishra, A., Gao, H., Liu, Y., Wenzel, P., Davis, B., Yoder, M. C., & Yoshimoto, M. (2019). Long-Term Engraftment of ESC-Derived B-1 Progenitor Cells Supports HSC-Independent Lymphopoiesis. Stem Cell Reports, 12(3), 572-583. https://doi.org/10.1016/j.stemcr.2019.01.006