Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors
Copyright policy )Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors
Cardiac progenitor cells (CPCs) must control their number and fate to sustain the rapid heart growth during development, yet the intrinsic factors and environment governing these processes remain unclear. Here, we show that deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs in second pharyngeal arches (PA2s) and is associated with an atrophic heart. With histological, flow cytometric and functional analyses, we find that CPCs remain undifferentiated and expansive in the PA2, but differentiate into cardiac cells as they exit the arch. Tracing of Nb- and Nbl-deficient CPCs by lineage-specific mosaicism reveals that the CPCs normally populate in the PA2, but lose their expansion potential in the PA2. These findings demonstrate that Nb and Nbl are intrinsic factors crucial for the renewal of CPCs in the PA2 and that the PA2 serves as a microenvironment for their expansion.
- UNSW Sydney Australia
- Oregon Health & Science University United States
- Yale University United States
- Cardiovascular Institute of the South United States
- Victor Chang Cardiac Research Institute Australia
570, QH301-705.5, Knockout, Science, 32 Biomedical and Clinical Sciences, Nerve Tissue Proteins, heart, Cardiovascular, self-renewal, Mice, anzsrc-for: 32 Biomedical and Clinical Sciences, cardiac progenitor, Animals, Cell Lineage, Myocytes, Cardiac, anzsrc-for: 31 Biological Sciences, Biology (General), Pediatric, numb, Mice, Knockout, Myocytes, anzsrc-for: 42 Health sciences, Mosaicism, Stem Cells, Q, anzsrc-for: 3201 Cardiovascular Medicine and Haematology, R, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Heart, Stem Cell Research, microenvironment, niche, Heart Disease, Developmental Biology and Stem Cells, 3201 Cardiovascular Medicine and Haematology, anzsrc-for: 0601 Biochemistry and Cell Biology, Medicine, Stem Cell Research - Nonembryonic - Non-Human, Cardiac, Gene Deletion, 31 Biological Sciences
570, QH301-705.5, Knockout, Science, 32 Biomedical and Clinical Sciences, Nerve Tissue Proteins, heart, Cardiovascular, self-renewal, Mice, anzsrc-for: 32 Biomedical and Clinical Sciences, cardiac progenitor, Animals, Cell Lineage, Myocytes, Cardiac, anzsrc-for: 31 Biological Sciences, Biology (General), Pediatric, numb, Mice, Knockout, Myocytes, anzsrc-for: 42 Health sciences, Mosaicism, Stem Cells, Q, anzsrc-for: 3201 Cardiovascular Medicine and Haematology, R, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Heart, Stem Cell Research, microenvironment, niche, Heart Disease, Developmental Biology and Stem Cells, 3201 Cardiovascular Medicine and Haematology, anzsrc-for: 0601 Biochemistry and Cell Biology, Medicine, Stem Cell Research - Nonembryonic - Non-Human, Cardiac, Gene Deletion, 31 Biological Sciences
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