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(xì)胞微環(huán)境

在成人心臟中已經(jīng)發(fā)現(xiàn)了心臟干細(xì)胞的存在,但是對(duì)于保護(hù)這些增殖緩慢、尚未分化但可自我更新的心臟干細(xì)胞的微環(huán)境，仍然有待研究。我們?cè)鴪?bào)道心肌層存在干細(xì)胞微環(huán)境組成的間質(zhì)結(jié)構(gòu)，其中包含可被溴脫氧尿嘧啶核苷長(zhǎng)期標(biāo)記的細(xì)胞。這些能長(zhǎng)期被標(biāo)記的細(xì)胞為心肌中存在心臟干細(xì)胞提供了功能依據(jù)，表明心臟是由干細(xì)胞層調(diào)控的器官。心臟微環(huán)境包含心臟干細(xì)胞和定向分化細(xì)胞，這兩種細(xì)胞又與心肌細(xì)胞和成纖維細(xì)胞等支持細(xì)胞相連。

在干細(xì)胞定向分化細(xì)胞與支持細(xì)胞交界處，連接素和鈣粘素構(gòu)成縫隙連接和黏合連接。心臟干細(xì)胞未分化狀態(tài)與a4整和素的表達(dá)同時(shí)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(xì)胞的分裂呈對(duì)稱以及不對(duì)稱兩種方式，而不對(duì)稱分裂居主要地位，心臟干細(xì)胞分裂后產(chǎn)生一個(gè)子代干細(xì)胞和一個(gè)定向分化的子細(xì)胞，通過這種生長(zhǎng)動(dòng)力學(xué)機(jī)制，原始的干細(xì)胞池得以維持,肌細(xì)胞和內(nèi)皮細(xì)胞及平滑肌細(xì)胞也一起產(chǎn)生。因此，整個(gè)心臟中干細(xì)胞調(diào)節(jié)心肌細(xì)胞的增殖是不同步的，即在心尖和心房部位較快，在中央?yún)^(qū)的基底和心室部較慢。

責(zé)任編輯：admin