Designing Motif-Engineered Receptors To Elucidate Signaling Molecules Important for Proliferation of Hematopoietic Stem Cells,ACS Synthetic Biology

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Designing Motif-Engineered Receptors To Elucidate Signaling Molecules Important for Proliferation of Hematopoietic Stem Cells
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-06-19 00:00:00 , DOI: 10.1021/acssynbio.8b00163
Shuta Ishizuka ₁ , Chen-Yi Lai ₂ , Makoto Otsu ₂ , Hiromitsu Nakauchi ₃ , Teruyuki Nagamune ₁ , Masahiro Kawahara ₁

Affiliation

The understanding of signaling events is critical for attaining long-term expansion of hematopoietic stem cells ex vivo. In this study, we aim to analyze the contribution of multiple signaling molecules in proliferation of hematopoietic stem cells. To this end, we design a bottom-up engineered receptor with multiple tyrosine motifs, which can recruit multiple signaling molecules of interest. This is followed by a top-down approach, where one of the multiple tyrosine motifs in the bottom-up engineered receptor is functionally knocked out by tyrosine-to-phenylalanine mutation. The combination of these two approaches demonstrates the importance of Shc in cooperation with STAT3 or STAT5 in the proliferation of hematopoietic stem cells. The platform developed herein may be applied for analyzing other cells and/or other cell fate regulation systems.

中文翻译：

设计基序工程化的受体，以阐明对于造血干细胞增殖重要的信号分子

对信号转导事件的理解对于离体造血干细胞的长期扩增至关重要。在这项研究中，我们旨在分析多种信号分子在造血干细胞增殖中的作用。为此，我们设计了一个具有多个酪氨酸基序的自下而上的工程受体，该受体可以募集感兴趣的多个信号分子。这之后是自上而下的方法，其中自下而上的工程受体中的多个酪氨酸基序之一在功能上被酪氨酸到苯丙氨酸突变敲除。这两种方法的结合证明了Shc与STAT3或STAT5协同作用在造血干细胞增殖中的重要性。本文开发的平台可以用于分析其他小区和/或其他小区命运调节系统。

更新日期：2018-06-19

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