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Genetic Lineage Tracing of Nonmyocyte Population by Dual Recombinases

Yan Li1, Lingjuan He1, Xiuzhen Huang1

  • 1The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, and Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, China (Yan Li, L.H., X.H., H.Z., S.Z., W.P., X.T., Yi Li, Q.L., W.Y., L.Z., X.L., K.L., J.T., H.Z., B.Z.).

Circulation
|April 28, 2018
PubMed

Insights

New research shows that non-heart muscle cells can become new heart muscle cells in embryonic hearts, but not in adult hearts. This finding challenges the idea of adult cardiac stem cells for heart regeneration.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Research
  • Regenerative Medicine

Background:

  • The existence of cardiac stem cells in adult mammalian hearts for cardiomyocyte regeneration remains a debated topic.
  • Previous studies have reported putative cardiac stem cell populations, identified by various markers (Sca1+, Bmi1+, Isl1+, Abcg2+) or lacking specific markers.
  • It is unclear if unidentified cardiac stem cells can generate new cardiomyocytes in the adult heart.

Purpose of the Study:

  • To investigate the potential of nonmyocytes to generate new cardiomyocytes in the adult heart without relying on specific stem cell markers.
  • To track cell lineages in vivo to determine the origin of new cardiomyocytes during embryonic development, adult homeostasis, and after myocardial infarction.

Main Methods:

  • Development of a novel, marker-free genetic lineage tracing system using dual recombinases.
  • Application of the system to track nonmyocyte populations in the embryonic and adult heart, as well as in skeletal muscle as a control.
  • Assessment of de novo cardiomyocyte generation from nonmyocytes under various physiological and pathological conditions.

Main Results:

  • Fate mapping data revealed that new cardiomyocytes arise from nonmyocytes in the embryonic heart.
  • No evidence of nonmyocyte-to-myocyte conversion was observed in the adult heart during homeostasis or following myocardial infarction.
  • The lineage tracing system successfully detected new myocyte generation from nonmyocytes in skeletal muscle after injury, serving as a positive control.

Conclusions:

  • This study provides in vivo genetic evidence that nonmyocyte to myocyte conversion occurs in the embryonic heart but not in the adult heart.
  • The findings challenge the myogenic potential of putative stem cell populations for cardiac regeneration in adult mammals.
  • A new genetic strategy for identifying endogenous stem cells in other organ systems for tissue repair is presented.
Abstract

Keywords:
cell lineagemyocardial infarctionmyocardial revascularizationmyocytes, cardiacrecombinasesstem cell

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