The selection of pluripotent stem cell (PSC)-derived cells for tissue modeling and cell therapy will be influenced by their response to the tissue environment, including the extracellular matrix (ECM). Whether and how instructive memory is imprinted in adult ECM and able to impact on the tissue specific determination of human PSC-derived developmentally fetal mesodermal precursor (P-meso) cells is investigated. Decellularized ECM (dECM) is generated from human heart, kidney, and lung tissues and recellularized with P-meso cells in a medium not containing any differentiation inducing components. While P-meso cells on kidney dECM differentiate exclusively into nephronal cells, only beating clusters containing mature and immature cardiac cells form on heart dECM. No tissue-specific differentiation of P-meso cells is observed on endoderm-derived lung dECM. P-meso-derived endothelial cells, however, are found on all dECM preparations independent of tissue origin. Clearance of heparan-sulfate proteoglycans (HSPG) from dECM abolishes induction of tissue-specific differentiation. It is concluded that HSPG-bound factors on adult tissue-derived ECM are essential and sufficient to induce tissue-specific specification of uncommitted fetal stage precursor cells.

中文翻译：

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成人组织细胞外基质决定了人类iPSC衍生的胚胎期中胚层前体细胞的组织规格。

用于组织建模和细胞治疗的多能干细胞（PSC）来源细胞的选择将受到其对组织环境（包括细胞外基质）的反应的影响。研究了在成人ECM中是否以及如何标记了指导性记忆，并且能够影响人PSC衍生的发育性胎儿中胚层前体（P-meso）细胞的组织特异性测定。脱细胞的ECM（dECM）是从人的心脏，肾脏和肺组织产生的，并在不包含任何诱导分化成分的培养基中用P-中胚层细胞再细胞化。肾脏dECM上的P-间充质细胞仅分化为肾细胞，而心脏dECM上仅形成含有成熟和未成熟心脏细胞的搏动簇。在内胚层来源的肺dECM上未观察到P-meso细胞的组织特异性分化。然而，在与组织来源无关的所有dECM制剂中都发现了P-meso来源的内皮细胞。从dECM中清除硫酸乙酰肝素蛋白聚糖（HSPG）消除了组织特异性分化的诱导。结论是，成年组织来源的ECM上与HSPG结合的因子至关重要，足以诱导未定居的胎儿阶段前体细胞的组织特异性。