Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.

An aligned, force‐generating, engineered cardiac patch was created using human induced pluripotent stem cell‐derived cardiomyocytes (CMs) and pericytes entrapped in a sacrificial fibrin gel. When transplanted onto acutely infarcted rat myocardium, the patch remained viable and CMs proliferated, resulting in improved cardiac function and reduced infarct size 4 weeks after transplantation, implicating potential paracrine‐based, infarct‐stabilizing mechanisms originating from the transplanted CMs.

The assimilation hypothesis argues that second language learning recruits the brain network for processing the native language, whereas the accommodation hypothesis argues that learning a second language recruits brain structures not involved in native language processing. This study tested these hypotheses by examining brain activation of a group of native Chinese speakers, who were late bilinguals with varying levels of proficiency in English, when they performed a rhyming judgment to visually presented English word pairs (CE group) during fMRI. Assimilation was examined by comparing the CE group to native Chinese speakers performing the rhyming task in Chinese (CC group), and accommodation was examined by comparing the CE group to native English speakers performing the rhyming task in English (EE group). The CE group was very similar in activation to the CC group, supporting the assimilation hypothesis. Additional support for the assimilation hypothesis was the finding that higher proficiency in the CE group was related to increased activation in the Chinese network (as defined by the CC > EE), including the left middle frontal gyrus, the right inferior parietal lobule, and the right precuneus, and decreased activation in the English network (as defined by the EE > CC), including the left inferior frontal gyrus and the left inferior temporal gyrus. Although most of the results support assimilation, there was some evidence for accommodation as the CE group showed less activation in the Chinese network including the right middle occipital gyrus, which has been argued to be involved in holistic visuospatial processing of Chinese characters.

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