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研究揭示钙离子对造血干细胞的维持作用
作者:小柯机器人 发布时间:2019/8/6 20:15:55

美国哥伦比亚大学欧文医学中心的Hans-Willem Snoeck研究组发现通过降低造血干细胞内钙离子可增加其在体外的维持。这一研究成果于2019年8月发表在国际学术期刊《细胞—干细胞》上。

研究人员发现,从表型、功能和单细胞表达特征等方面来看,低钙培养的造血干细胞能够增加其维持。由于糖酵解供能的质膜钙离子流泵的活性提高,以及骨髓间质液的低钙离子浓度,HSC具有较低的胞内钙离子。低钙条件抑制了钙蛋白酶活性,而钙蛋白酶可抑制TET酶,而其中的TET2又是低钙条件下HSC的体外维持所需。这些发现揭示了HSC的一种生理特性,并可以用来改善它们在体外的维持。

据悉,造血干细胞(HSC)独特的细胞生理性还尚未研究清楚,而其在体外的维持仍然具有挑战性。



附:英文原文

Title: Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro

Author: Larry L. Luchsinger, Alexandros Strikoudis, Nichole M. Danzl, Erin C. Bush, Michael O. Finlayson, Prakash Satwani, Megan Sykes, Masayuki Yazawa, Hans-Willem Snoeck

Issue&Volume: Volume 25 Issue 2

Abstract: The specific cellular physiology of hematopoietic stem cells (HSCs) is underexplored, and their maintenance in vitro remains challenging. We discovered that culture of HSCs in low calcium increased their maintenance as determined by phenotype, function, and single-cell expression signature. HSCs are endowed with low intracellular calcium conveyed by elevated activity of glycolysis-fueled plasma membrane calcium efflux pumps and a low-bone-marrow interstitial fluid calcium concentration. Low-calcium conditions inhibited calpain proteases, which target ten-eleven translocated (TET) enzymes, of which TET2 was required for the effect of low calcium conditions on HSC maintenance in vitro. These observations reveal a physiological feature of HSCs that can be harnessed to improve their maintenance in vitro.

DOI: https://doi.org/10.1016/j.stem.2019.05.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30206-1

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx