Abstract
Cardiac stem cells (CSCs) have been identified in the adult heart but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and f ibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs-lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of α4-integrin, which colocalizes with the α2-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base-midregion of the ventricle.
| Original language | English |
|---|---|
| Pages (from-to) | 9226-9231 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 103 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - Jun 13 2006 |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
Stem cell niches in the adult mouse heart. / Urbanek, Konrad; Cesselli, Daniela; Rota, Marcello; Nascimbene, Angelo; De Angelis, Antonella; Hosoda, Toru; Bearzi, Claudia; Boni, Alessandro; Bolli, Roberto; Kajstura, Jan; Anversa, Piero; Leri, Annarosa.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 24, 13.06.2006, p. 9226-9231.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stem cell niches in the adult mouse heart
AU - Urbanek, Konrad
AU - Cesselli, Daniela
AU - Rota, Marcello
AU - Nascimbene, Angelo
AU - De Angelis, Antonella
AU - Hosoda, Toru
AU - Bearzi, Claudia
AU - Boni, Alessandro
AU - Bolli, Roberto
AU - Kajstura, Jan
AU - Anversa, Piero
AU - Leri, Annarosa
PY - 2006/6/13
Y1 - 2006/6/13
N2 - Cardiac stem cells (CSCs) have been identified in the adult heart but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and f ibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs-lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of α4-integrin, which colocalizes with the α2-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base-midregion of the ventricle.
AB - Cardiac stem cells (CSCs) have been identified in the adult heart but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and f ibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs-lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of α4-integrin, which colocalizes with the α2-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base-midregion of the ventricle.
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U2 - 10.1073/pnas.0600635103
DO - 10.1073/pnas.0600635103
M3 - Article
C2 - 16754876
AN - SCOPUS:33745130013
VL - 103
SP - 9226
EP - 9231
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 24
ER -