Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 16635-148, Iran.
Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111, Iran.
J Proteome Res. 2020 Dec 4;19(12):4747-4753. doi: 10.1021/acs.jproteome.0c00689. Epub 2020 Oct 30.
The Chromosome-Centric Human Proteome Project (C-HPP) aims at the identification of missing proteins (MPs) and the functional characterization of functionally unannotated PE1 (uPE1) proteins. A major challenge in addressing this goal is that many human proteins and MPs are silent in adult cells. A promising approach to overcome such challenge is to exploit the advantage of novel tools such as pluripotent stem cells (PSCs), which are capable of differentiation into three embryonic germ layers, namely, the endoderm, mesoderm, and ectoderm. Here we present several examples of how the Human Y Chromosome Proteome Project (Y-HPP) benefited from this approach to meet C-HPP goals. Furthermore, we discuss how integrating CRISPR engineering, human-induced pluripotent stem cell (hiPSC)-derived disease modeling systems, and organoid technologies provides a unique platform for Y-HPP and C-HPP for MP identification and the functional characterization of human proteins, especially uPE1s.
染色体为中心的人类蛋白质组计划（C-HPP）旨在鉴定缺失蛋白（MPs）和功能注释的非主要外显子 1（uPE1）蛋白的功能特征。实现这一目标的主要挑战之一是，许多人类蛋白质和 MPs 在成年细胞中是沉默的。克服这一挑战的一个有希望的方法是利用多能干细胞（PSCs）等新工具的优势，PSCs 能够分化为三个胚胎原基，即内胚层、中胚层和外胚层。本文介绍了人类 Y 染色体蛋白质组计划（Y-HPP）如何受益于这一方法来实现 C-HPP 目标的几个例子。此外，我们还讨论了如何将 CRISPR 工程、人诱导多能干细胞（hiPSC）衍生的疾病建模系统和类器官技术集成到一起，为 Y-HPP 和 C-HPP 提供了一个独特的平台，用于鉴定 MPs 和人类蛋白质，特别是 uPE1s 的功能特征。
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