Russian Journal of Developmental BiologyRussian Journal of Developmental Biology0475-14503034-6266Russian Academy of Science10.31857/S047514502301010XThe Role of Extracellular Matrix in Human Pluripotent Cells Differentiation into Ectodermal DerivativesРоль компонентов внеклеточного матрикса в дифференцировке эктодермальных производных плюрипотентных клеток человекаOgnivtsevA. A.ОгнивцевА. А. Kalabusheva.e@gmail.comИнститут биологии развития им. Н.К. Кольцова РАНKoltzov Institute of Developmental Biology of the Russian Academy of Sciences010120235414158

One of the most important events in the embryonic development of mammals is the division of the ectoderm into integumentary and neuroectoderm. Signaling cascades induced by growth factors and cytokines involved in these processes have been studied in detail in recent decades. At the same time, the contribution of extracellular matrix (ECM) to these differentiation lineages remains unknown for mammals, while the significance of ECM in this process has been shown in other model organisms. To assess the effect of ECM on the formation of ectodermal derivatives, we modeled the neural and epidermal differentiation of human induced pluripotent stem cells (iPSCs) using substrates consisting of various ECM molecules; and also studied the involvement of one of the central links of the ECM signaling cascades, a transcriptional coactivator YAP1 in differentiation processes. Our results revealed the stimulatory effect of laminin 332 on the early stages of epidermal differentiation and of type I and III collagens on the inducing of the glial fate of late neural differentiation.

Одним из важнейших событий эмбрионального развития млекопитающих является разделение эктодермы на покровную и нейроэктодерму. Сигнальные каскады, индуцируемые факторами роста и цитокинами, вовлеченными в эти процессы, детально изучаются последние десятилетия. В то же время вклад компонентов внеклеточного матрикса (ВКМ) в эти направления дифференцировки остается неизвестным для млекопитающих, в то время как важнейшая роль ВКМ в этом процессе показана на других модельных организмах. Для оценки влияния компонентов ВКМ на формирование эктодермальных производных мы моделировали нейральную и эпидермальную дифференцировку индуцированных плюрипотентных стволовых клеток (ИПСК) человека с использованием субстратов, состоящих из различных компонентов ВКМ, а также исследовали вовлеченность в процессы дифференцировки одного из центральных звеньев сигнальных каскадов ВКМ, транскрипционного коактиватора YAP1. Наши результаты выявили стимулирующий эффект ламинина 332 на ранние этапы эпидермальной дифференцировки и коллагенов I и III типов на выделение глиального направления поздней нейральной дифференцировки.

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