Self-organizing human cardiac microchambers mediated by geometric confinement.
Self-organizing human cardiac microchambers mediated by geometric confinement.
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DOI：
10.1038/ncomms8413
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发表时间：
2015-07-14
影响因子：
16.6
通讯作者：
Healy KE
中科院分区：
文献类型：
--
作者：
Ma Z;Wang J;Loskill P;Huebsch N;Koo S;Svedlund FL;Marks NC;Hua EW;Grigoropoulos CP;Conklin BR;Healy KE
Tissue morphogenesis and organ formation are the consequences of biochemical and biophysical cues that lead to cellular spatial patterning in development. To model such events in vitro, we use PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promotes spatial patterning via geometric confinement of the cell condensation process during epithelial–mesenchymal transition, forcing cells at the perimeter to express an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induce self-organizing lineage specification and creation of a beating human cardiac microchamber confined by the pattern geometry. These highly defined human cardiac microchambers can be used to study aspects of embryonic spatial patterning, early cardiac development and drug-induced developmental toxicity. Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells' differentiation into beating cardiac microchambers resembling primitive hearts.
