Francois E Mercier

Massachusetts General Hospital, Boston, Massachusetts, United States

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Publications (7)176.3 Total impact

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    ABSTRACT: Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol. Using these methods we achieved ∼75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens.
    Nature Biotechnology 09/2015; 33(10). DOI:10.1038/nbt.3354 · 41.51 Impact Factor
  • Francois Mercier · Jiantao Shi · David Sykes · Youmna Kfoury · David Scadden
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    Youmna Kfoury · Francois Mercier · David T Scadden
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    ABSTRACT: The bone marrow microenvironment regulates hematopoietic stem cell (HSC) function and protects HSCs from exhaustion. Technological advances have expanded understanding of the microenvironment's structural and functional organization. Here, we describe three major HSC niche components: the endosteal zone, the vasculature, and hematopoietic progeny. Roles for the microenvironment in HSC mobilization and in malignancy are presented.
    Cell 07/2014; 158(1):228-228.e1. DOI:10.1016/j.cell.2014.06.019 · 32.24 Impact Factor
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    ABSTRACT: X chromosome aneuploidies have long been associated with human cancers, but causality has not been established. In mammals, X chromosome inactivation (XCI) is triggered by Xist RNA to equalize gene expression between the sexes. Here we delete Xist in the blood compartment of mice and demonstrate that mutant females develop a highly aggressive myeloproliferative neoplasm and myelodysplastic syndrome (mixed MPN/MDS) with 100% penetrance. Significant disease components include primary myelofibrosis, leukemia, histiocytic sarcoma, and vasculitis. Xist-deficient hematopoietic stem cells (HSCs) show aberrant maturation and age-dependent loss. Reconstitution experiments indicate that MPN/MDS and myelofibrosis are of hematopoietic rather than stromal origin. We propose that Xist loss results in X reactivation and consequent genome-wide changes that lead to cancer, thereby causally linking the X chromosome to cancer in mice. Thus, Xist RNA not only is required to maintain XCI but also suppresses cancer in vivo.
    Cell 02/2013; 152(4):727-42. DOI:10.1016/j.cell.2013.01.034 · 32.24 Impact Factor
  • Francois E Mercier · Christine Ragu · David T Scadden
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    ABSTRACT: Progenitor cells that are the basis for all blood cell production share the bone marrow with more mature elements of the adaptive immune system. Specialized niches within the bone marrow guide and, at times, constrain the development of haematopoietic stem and progenitor cells (HSPCs) and lineage-restricted immune progenitor cells. Specific niche components are organized into distinct domains to create a diversified landscape in which specialized cell differentiation or population expansion programmes proceed. Local cues that reflect the tissue and organismal state affect cellular interactions to alter the production of a range of cell types. Here, we review the organization of regulatory elements in the bone marrow and discuss how these elements provide a dynamic means for the host to modulate stem cell and adaptive immune cell responses to physiological challenges.
    Nature Reviews Immunology 12/2011; 12(1):49-60. DOI:10.1038/nri3132 · 34.99 Impact Factor
  • François Mercier · Marie-Christine Guiot · Michel W Bojanowski
    Journal of Neuro-Oncology 11/2011; 107(2):435-7. DOI:10.1007/s11060-011-0767-2 · 3.07 Impact Factor
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    ABSTRACT: AKT activation is associated with many malignancies, where AKT acts, in part, by inhibiting FOXO tumor suppressors. We show a converse role for AKT/FOXOs in acute myeloid leukemia (AML). Rather than decreased FOXO activity, we observed that FOXOs are active in ∼40% of AML patient samples regardless of genetic subtype. We also observe this activity in human MLL-AF9 leukemia allele-induced AML in mice, where either activation of Akt or compound deletion of FoxO1/3/4 reduced leukemic cell growth, with the latter markedly diminishing leukemia-initiating cell (LIC) function in vivo and improving animal survival. FOXO inhibition resulted in myeloid maturation and subsequent AML cell death. FOXO activation inversely correlated with JNK/c-JUN signaling, and leukemic cells resistant to FOXO inhibition responded to JNK inhibition. These data reveal a molecular role for AKT/FOXO and JNK/c-JUN in maintaining a differentiation blockade that can be targeted to inhibit leukemias with a range of genetic lesions.
    Cell 09/2011; 146(5):697-708. DOI:10.1016/j.cell.2011.07.032 · 32.24 Impact Factor

Publication Stats

255 Citations
176.30 Total Impact Points


  • 2011–2014
    • Massachusetts General Hospital
      • Center for Regenerative Medicine
      Boston, Massachusetts, United States
    • Harvard University
      • Department of Stem Cell and Regenerative Biology
      Cambridge, Massachusetts, United States