Stem cell niches in the adult mouse heart
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 adherentj unctions at the interface of CSCs lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of a4-integrin,which colocalizes with the a2-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 preservedand 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.
[Proc Natl Acad Sci USA,2006;103(24), 9226-9231]
成年鼠心臟的干細胞微環(huán)境
在成人心臟中已經發(fā)現了心臟干細胞的存在,但是對于保護這些增殖緩慢、尚未分化但可自我更新的心臟干細胞的微環(huán)境，仍然有待研究。我們曾報道心肌層存在干細胞微環(huán)境組成的間質結構，其中包含可被溴脫氧尿嘧啶核苷長期標記的細胞。這些能長期被標記的細胞為心肌中存在心臟干細胞提供了功能依據，表明心臟是由干細胞層調控的器官。心臟微環(huán)境包含心臟干細胞和定向分化細胞，這兩種細胞又與心肌細胞和成纖維細胞等支持細胞相連。
在干細胞定向分化細胞與支持細胞交界處，連接素和鈣粘素構成縫隙連接和黏合連接。心臟干細胞未分化狀態(tài)與a4整和素的表達同時存在，4整和素與層粘連蛋白和纖維連接蛋白的a2鏈定位于相同位置。心臟干細胞的分裂呈對稱以及不對稱兩種方式，而不對稱分裂居主要地位，心臟干細胞分裂后產生一個子代干細胞和一個定向分化的子細胞，通過這種生長動力學機制，原始的干細胞池得以維持,肌細胞和內皮細胞及平滑肌細胞也一起產生。因此，整個心臟中干細胞調節(jié)心肌細胞的增殖是不同步的，即在心尖和心房部位較快，在中央區(qū)的基底和心室部較慢。
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