Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells

Janina Ratajczak, Marcin Wysoczynski, Ewa Zuba-Surma, Wu Wan, Magda Kucia, Mervin Yoder, Mariusz Z. Ratajczak

Research output: Contribution to journalArticle

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Abstract

Objective: We recently identified a population of small Sca-1+/Lin-/CD45- cells in adult murine bone marrow that express several epiblast/germ line and pluripotent stem cell markers (e.g., Oct-4 and SSEA-4) that we named " very small embryonic-like stem cells" (VSELs). In this report, we test the hypothesis that VSELs can differentiate along the hemato/lymphopoietic lineage. Materials and Methods: Purified from bone marrow, VSELs were primed/cocultured over OP9 stroma cell line and subsequently tested in vitro and in vivo assays for their hematopoietic potential. In parallel, cells derived from VSELs were evaluated for expression of hematopoietic genes and surface markers. Results: Although we observed that freshly isolated VSELs do not exhibit in vitro and in vivo hematopoietic potential, they may, after coculture over OP9 stromal cells, differentiate along the hematopoietic lineage in a similar way as embryonic stem cells or inducible pluripotent stem cells. " OP9-primed," VSEL-derived cells acquired expression of several hemato/lymphopoiesis-specific genes and markers, gave rise to hematopoietic colonies in vitro, and protected lethally irradiated mice in both primary and secondary transplant models on transplantation. We also observed that, compared to hematopoietic stem/progenitor cells, VSELs are highly resistant to total body irradiation. Conclusions: Based on these observations, we postulate that VSELs are the most primitive murine bone marrow-residing population of stem cells that have the potential to become specified into the hematopoietic lineage and may share some of the characteristics of long-term repopulating HSCs.

Original languageEnglish
Pages (from-to)225-237
Number of pages13
JournalExperimental Hematology
Volume39
Issue number2
DOIs
StatePublished - Feb 2011

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Embryonic Stem Cells
Stromal Cells
Coculture Techniques
Pluripotent Stem Cells
Bone Marrow
Hematopoietic Stem Cells
Lymphopoiesis
Germ Layers
Whole-Body Irradiation
Germ Cells
Population
Stem Cells
Transplantation
Transplants
Gene Expression
Cell Line
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

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Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells. / Ratajczak, Janina; Wysoczynski, Marcin; Zuba-Surma, Ewa; Wan, Wu; Kucia, Magda; Yoder, Mervin; Ratajczak, Mariusz Z.

In: Experimental Hematology, Vol. 39, No. 2, 02.2011, p. 225-237.

Research output: Contribution to journalArticle

Ratajczak, Janina ; Wysoczynski, Marcin ; Zuba-Surma, Ewa ; Wan, Wu ; Kucia, Magda ; Yoder, Mervin ; Ratajczak, Mariusz Z. / Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells. In: Experimental Hematology. 2011 ; Vol. 39, No. 2. pp. 225-237.
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