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Mds1CreER, a New Inducible Cre Allele Specific to Adult-Repopulating Hematopoietic Stem Cells

27 Pages Posted: 3 Jun 2020 Publication Status: Published

See all articles by Yi Zhang

Yi Zhang

University of Rochester - Department of Pathology and Laboratory Medicine

Kathleen E. McGrath

University of Rochester - Center for Pediatric Biomedical Research

Edward Ayoub

University of Rochester - Department of Pathology and Laboratory Medicine

Paul D. Kingsley

University of Rochester - Center for Pediatric Biomedical Research

Hongbo Yu

VA Boston Healthcare System - Department of Pathology and Laboratory Medicine

Kate Fegan

University of Rochester - Center for Pediatric Biomedical Research

Kelly A. McGlynn

University of Rochester - Department of Pathology and Laboratory Medicine

Sarah Rudzinskas

University of Rochester - Department of Pathology and Laboratory Medicine

James Palis

University of Rochester - Center for Pediatric Biomedical Research

Archibald S. Perkins

University of Rochester - Department of Pathology and Laboratory Medicine

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Abstract

Hematopoietic ontogeny consists of two broad programs: an initial hematopoietic stem cell (HSC)-independent program arising from the yolk sac followed by HSC-dependent hematopoiesis arising from intra-embryonic arteries. While HSC-independent erythro-myeloid (EMP) progenitors and rare lymphoid progenitors, as well as HSCs, sequentially seed the fetal liver and generate blood cells, the transition from HSC-independent to HSC-derived hematopoiesis remains poorly characterized. To help resolve this question, we developed Mds1CreER mice, which inducibly express Cre-recombinase specifically in HSCs. Our lineage tracing studies indicate that HSC-derived progeny significantly expand in the liver between E14.5-E16.5. Additionally, we find that HSCs contribute the majority of F4/80+ macrophages in adult spleen and marrow, in contrast to their limited contribution to macrophage populations in brain, liver and lungs. The Mds1CreER mouse model will be useful to deconvolute the complexity of hematopoiesis as it unfolds in the embryo and functions postnatally.

Keywords: embryonic hematopoiesis, hematopoietic stem cell, mouse model for lineage tracing, ontogeny of tissue-based macrophages

Suggested Citation

Zhang, Yi and McGrath, Kathleen E. and Ayoub, Edward and Kingsley, Paul D. and Yu, Hongbo and Fegan, Kate and McGlynn, Kelly A. and Rudzinskas, Sarah and Palis, James and Perkins, Archibald S., Mds1CreER, a New Inducible Cre Allele Specific to Adult-Repopulating Hematopoietic Stem Cells. Available at SSRN: https://ssrn.com/abstract=3599023 or http://dx.doi.org/10.2139/ssrn.3599023
This version of the paper has not been formally peer reviewed.

Yi Zhang

University of Rochester - Department of Pathology and Laboratory Medicine

United States

Kathleen E. McGrath

University of Rochester - Center for Pediatric Biomedical Research

300 Crittenden Blvd.
Rochester, NY 14627
United States

Edward Ayoub

University of Rochester - Department of Pathology and Laboratory Medicine

United States

Paul D. Kingsley

University of Rochester - Center for Pediatric Biomedical Research

300 Crittenden Blvd.
Rochester, NY 14627
United States

Hongbo Yu

VA Boston Healthcare System - Department of Pathology and Laboratory Medicine ( email )

Boston, MA
United States

Kate Fegan

University of Rochester - Center for Pediatric Biomedical Research

300 Crittenden Blvd.
Rochester, NY 14627
United States

Kelly A. McGlynn

University of Rochester - Department of Pathology and Laboratory Medicine

United States

Sarah Rudzinskas

University of Rochester - Department of Pathology and Laboratory Medicine

United States

James Palis

University of Rochester - Center for Pediatric Biomedical Research ( email )

300 Crittenden Blvd.
Rochester, NY 14627
United States

Archibald S. Perkins (Contact Author)

University of Rochester - Department of Pathology and Laboratory Medicine ( email )

United States

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