2026-04-29T16:55:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52602024-09-27T09:38:12Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Valiente-Alandi, I
author
Albo-Castellanos, Carmen
author
Herrero, Diego
author
Arza, Elvira
author
Garcia-Gomez, Maria
author
Segovia, Jose Carlos
author
Capecchi, Mario
author
Bernad, Antonio
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea
funder
Ministerio de Economía y Competitividad (España)
2017-10-30T13:32:28Z
2017-10-30T13:32:28Z
2015
Stem Cell Res Ther. 2015; 6:205
10.1186/s13287-015-0196-9
1757-6512
Stem Cell Research & Therapy
26503423
http://hdl.handle.net/20.500.12105/5260
Introduction: The mammalian adult heart maintains a continuous, low cardiomyocyte turnover rate throughout life. Although many cardiac stem cell populations have been studied, the natural source for homeostatic repair has not yet been defined. The Polycomb protein BMI1 is the most representative marker of mouse adult stem cell systems. We have evaluated the relevance and role of cardiac Bmi1(+) cells in cardiac physiological homeostasis. Methods: Bmi1(CreER/+); Rosa26(YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy. After tamoxifen (TM) induction, yellow fluorescent protein (YFP) is expressed under the control of Rosa26 regulatory sequences in Bmi1(+) cells. These cells and their progeny were tracked by FACS, immunofluorescence and RT-qPCR techniques from 5 days to 1 year. Results: FACS analysis of non-cardiomyocyte compartment from TM-induced Bmi1-YFP mice showed a Bmi1 (+)-expressing cardiac progenitor cell (Bmi1-CPC: B-CPC) population, SCA-1 antigen-positive (95.9 +/- 0.4 \%) that expresses some stemness-associated genes. B-CPC were also able to differentiate in vitro to the three main cardiac lineages. Pulse-chase analysis showed that B-CPC remained quite stable for extended periods (up to 1 year), which suggests that this Bmi1(+) population contains cardiac progenitors with substantial self-maintenance potential. Specific immunostaining of Bmi1-YFP hearts serial sections 5 days post-TM induction indicated broad distribution of B-CPC, which were detected in variably sized clusters, although no YFP+ cardiomyocytes (CM) were detected at this time. Between 2 to 12 months after TM induction, YFP+ CM were clearly identified (3 +/- 0.6 \% to 6.7 +/- 1.3 \%) by immunohistochemistry of serial sections and by flow cytometry of total freshly isolated CM. B-CPC also contributed to endothelial and smooth muscle (SM) lineages in vivo. Conclusions: High Bmi1 expression identifies a non-cardiomyocyte resident cardiac population (B-CPC) that contributes to the main lineages of the heart in vitro and in vivo.
eng
Heart homeostasis
Stem cells
Bmi1
Cardiac progenitor cells
HEMATOPOIETIC STEM-CELLS
CARDIOSPHERE-DERIVED CELLS
SELF-RENEWAL
ORGAN HOMEOSTASIS
MAMMALIAN HEART
MOUSE HEART
REGENERATION
PROGENITORS
INFARCTION
BMI-1
Cardiac Bmi1(+) cells contribute to myocardial renewal in the murine adult heart
journal article
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CardiacBmi1+CellsContribute_2015.pdf
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CardiacBmi1+CellsContribute_2015.pdf.txt