Stem cell niches in the adult mouse heart
Stem cell niches in the adult mouse heart
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DOI：
10.1073/pnas.0600635103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Leri, Annarosa
中科院分区：
文献类型：
--
作者：
Urbanek, Konrad;Cesselli, Daniela;Leri, Annarosa
已在成人心脏中鉴定出心脏干细胞（CSCs），但保护慢循环、未分化和自我更新的CSCs的微环境仍有待确定。我们报告说，心肌具有间质结构与建筑组织的干细胞壁龛，港口长期BrdU滞留细胞。长期标记保留细胞的识别提供了心肌中常驻CSC的功能证据，表明心脏是由干细胞隔室调节的器官。心脏小生境包含CSC和谱系定向细胞，其连接到以肌细胞和成纤维细胞为代表的支持细胞。缝隙连接蛋白和钙粘蛋白在CSC谱系定向细胞和支持细胞的界面形成缝隙连接和粘附连接。CSC的未分化状态与α 4-整联蛋白的表达相关，α 4-整联蛋白与层粘连蛋白和纤连蛋白的α（2）-链共定位。CSC分裂对称和不对称，但不对称分裂占主导地位，并复制CSC产生一个女儿CSC和一个女儿定向细胞。通过这种生长动力学机制，原始CSC库得以保存，并且与内皮细胞和平滑肌细胞一起产生肌细胞后代。因此，CSC调节的心肌细胞更新在整个心脏中是异质的，在心尖和心房更快，在心室的基部-中部区域更慢。
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 fibroblasts. 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 alpha 4-integrin, which colocalizes with the alpha(2)-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.