Abstract
Abcg2, a member of the ATP-binding cassette transporter family, is expressed in adult hematopoietic stem cells (HSCs) and is required for the side population phenotype of adult bone marrow HSCs and other adult tissue-specific stem cells. Lineage tracing in adult mice using the Abcg2-Cre mouse model showed that Abcg2 marks HSCs, intestinal stem cells, and spermatogonial stem cells. It is unclear whether definitive HSCs or their precursors in early embryonic development can be marked by Abcg2 expression. Here, we treated pregnant Abcg2 Cre/Cre RosaLSL-YFP mice with a single injection of 4-hydroxytamoxifen at embryonic day 7.5. Four months after birth, a small yellow fluorescent protein-positive (YFP+) cell population could be detected in all of the major white blood cell lineages and this was stable for 8 months. Transplant of bone marrow cells or Sca1+YFP+ cells from these mice showed continued multilineage marking in recipient mice at 4 months. These results demonstrate that Abcg2 expression marks precursors to adult long-term repopulating HSCs at E7.5 to E8.5 and contributes to a stable subpopulation of HSCs well into adulthood.
Highlights
Abcg2 is a plasma membrane transporter that is expressed in the side population cells of a variety of tissues, including cancer cells, and is required for their SP phenotype [1,2]
Upon exposure to 4-OHT, the Cre translocates to the nucleus and deletes the stop element upstream of the EYFP transgene, which leads to ubiquitous, permanent expression of yellow fluorescent protein (YFP) in all progenies
We have shown that hematopoietic stem cells (HSCs) development was normal in the Abcg2À/À mice [6], so hematopoietic development is most likely unperturbed in the Abcg2CreERT2RosaEYFP mouse model
Summary
Abcg2 is a plasma membrane transporter that is expressed in the side population cells of a variety of tissues, including cancer cells, and is required for their SP phenotype [1,2]. Transplantation Sca1+ cells were first enriched from bone marrow of selected mice that were treated with 4-OHT at E7.5 and were 9 months of age at that time. Single pulse treatment of mice with 4-OHT at E7.5 marks pdHSCs In our lineage-tracing mouse model, the CreERT2 was coexpressed with endogenous Abcg2 because the IresCreERT2 expression cassette is inserted downstream of the Abcg2 coding sequence [4].
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