小柯机器人

切换到桌面版
分区的代谢支持孕中期哺乳动物的发育
2022-04-10 14:04
来源：小柯机器人

美国德克萨斯大学Ralph J. DeBerardinis团队发现，分区的代谢支持孕中期哺乳动物的发育。该项研究成果于2022年4月6日在线发表在《自然》杂志上。

研究人员使用同位素追踪和代谢组学来确定了小鼠孕中期胎盘和胚胎中不断变化的代谢程序。这些组织在整个孕中期都有不同的代谢，但研究人员把妊娠天数（GD）10.5-11.5确定为胎盘和胚胎的过渡期。同位素追踪显示了组织间碳水化合物代谢的差异和快速的葡萄糖依赖性嘌呤合成，特别是在胚胎中。葡萄糖对三羧酸（TCA）循环的贡献在胚胎整个孕中期上升，但在胎盘中没有。到GD12.5时，胚胎内明显出现了分区的代谢程序，包括不同器官对TCA循环的不同营养贡献。
 
为了了解与孟德尔代谢缺陷有关的发育异常情况，研究人员分析了LIPT1的缺陷小鼠，这种酶激活与TCA循环有关的2-酮酸脱氢酶。LIPT1的缺乏抑制了GD10.5-GD11.5过渡期的TCA循环代谢，扰乱了大脑、心脏和红细胞的发育，并导致了GD11.5的胚胎死亡。这些数据记录了子宫内发育器官的个体化代谢程序。
 
据介绍，哺乳动物的胚胎发育需要快速生长和适当的代谢调节。孕中期的特点是伴随着胎儿器官的发育，氧气和营养物质的供应不断增加。了解新陈代谢如何支持发育需要有直接观察子宫内模型生物新陈代谢的方法。
 
附：英文原文
 
Title: Compartmentalized metabolism supports midgestation mammalian development

Author: Solmonson, Ashley, Faubert, Brandon, Gu, Wen, Rao, Aparna, Cowdin, Mitzy A., Menendez-Montes, Ivan, Kelekar, Sherwin, Rogers, Thomas J., Pan, Chunxiao, Guevara, Gerardo, Tarangelo, Amy, Zacharias, Lauren G., Martin-Sandoval, Misty S., Do, Duyen, Pachnis, Panayotis, Dumesnil, Dennis, Mathews, Thomas P., Tasdogan, Alpaslan, Pham, An, Cai, Ling, Zhao, Zhiyu, Ni, Min, Cleaver, Ondine, Sadek, Hesham A., Morrison, Sean J., DeBerardinis, Ralph J.

Issue&Volume: 2022-04-06

Abstract: Mammalian embryogenesis requires rapid growth and proper metabolic regulation1. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development2,3. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero. Here we used isotope tracing and metabolomics to identify evolving metabolic programmes in the placenta and embryo during midgestation in mice. These tissues differ metabolically throughout midgestation, but we pinpointed gestational days (GD) 10.5–11.5 as a transition period for both placenta and embryo. Isotope tracing revealed differences in carbohydrate metabolism between the tissues and rapid glucose-dependent purine synthesis, especially in the embryo. Glucose’s contribution to the tricarboxylic acid (TCA) cycle rises throughout midgestation in the embryo but not in the placenta. By GD12.5, compartmentalized metabolic programmes are apparent within the embryo, including different nutrient contributions to the TCA cycle in different organs. To contextualize developmental anomalies associated with Mendelian metabolic defects, we analysed mice deficient in LIPT1, the enzyme that activates 2-ketoacid dehydrogenases related to the TCA cycle4,5. LIPT1 deficiency suppresses TCA cycle metabolism during the GD10.5–GD11.5 transition, perturbs brain, heart and erythrocyte development and leads to embryonic demise by GD11.5. These data document individualized metabolic programmes in developing organs in utero.

DOI: 10.1038/s41586-022-04557-9

Source: https://www.nature.com/articles/s41586-022-04557-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

分享到:

0