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IF45.8!全球首发!江西农业大学首个猪单细胞图谱登顶《Science》!揭示妊娠心脏及生长受限!

  • 2026-05-09 03:36:50
IF45.8!全球首发!江西农业大学首个猪单细胞图谱登顶《Science》!揭示妊娠心脏及生长受限!

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🔈妊娠是母体与胎儿共同经历的复杂生理过程,其调控机制的解析对改善围产期健康至关重要。

江西农业大学黄路生院士团队《Science》期刊上发表的题为“家族单细胞图谱揭示了猪怀孕和胎儿生长受限的关键细胞类型”的文章,构建了猪全身单细胞图谱,揭示了孕期心脏适应性重塑及亮氨酸转运不足导致胎儿生长受限的关键机制。📝

标题家族单细胞图谱揭示了猪怀孕和胎儿生长受限的关键细胞类型

发表期刊:Science

发表时间:2026年

影响因子:45.8/Q1

01

研究背景

孕妇心脏样本获取困难,限制孕期心血管适应研究;FGR 高发且危害围产健康,猪与人生理基因组相似度高、FGR 发生率更高,是理想研究模型。

02

研究目的

本研究旨在构建孕母胎全身单细胞图谱,解析孕期心脏适应性重塑的细胞机制,阐明胎儿生长受限的细胞分子基础,并验证核心发现在人与小鼠间的跨物种保守性(图1)

图1.单一家系猪全域单细胞图谱

03

研究方法亮点

1️⃣“单一个体全覆盖”设计:避免遗传、年龄、环境等混杂因素。

2️⃣快速组织处理:入6小时内完成275个组织的采样与解离。

3️⃣多组学整合:scRNA-seq、snRNA-seq、代谢组、体外类器官、基因编辑动物模型。

4️⃣跨物种验证:整合人类与小鼠单细胞数据,验证关键细胞类型的保守性。

1、全身单细胞图谱概览

本研究整合胎儿115个组织、母体119个组织共256万个细胞,构建全域单细胞图谱;经UMAP解析76类细胞全身分布,明晰器官细胞共性与特异性,为相关转录因子研究奠基,建成首个单一个体全覆盖猪单细胞全景图谱(图2)

图2.两猪家系全域单细胞图谱总览图

2内皮细胞异质性与转录因子解析

内皮细胞亚型存在显著器官差异;脑部内皮细胞免疫基因低表达,凸显血脑屏障免疫特性,各器官毛细血管内皮特异表达代谢相关受体,整体具备强器官特异性(图3)

图3.全域单细胞图谱与猪全身内皮细胞解析图

研究鉴定了胎儿与成年猪大量细胞特异性转录因子;IRX6为跨脑区保守的小胶质细胞特异转录因子,经基因编辑与ATAC‑seq验证,可调控其突触修剪与免疫功能(图4)

图4.59种器官中内皮细胞的器官内异质性与免疫调控功能差异

3组织特异转录因子识别验证

研究鉴定胎儿355个、成年407 个特异性转录因子;IRX6在11个脑区保守特异表达,经基因编辑猪与ATAC-seq验证,可调控小胶质细胞突触修剪与细胞分泌,是跨脑区、跨发育阶段介导免疫与神经发育的关键因子图5)

图5.特异性转录因子鉴定与表征标准化表达热图

4妊娠期心脏毛细血管内皮

妊娠晚期心脏特异富集Cap2内皮亚型,高表达脂肪酸转运基因、低表达糖转运基因,且孕期升高、产后可逆;相关基因可增强脂肪酸摄取,是母体适配能量需求的生理调控机制图6)

图6.猪心孕期细胞与功能动态变化

5亮氨酸缺乏抑制胎儿肌纤维发育

胎儿生长受限源于胎盘氨基酸转运蛋白下调,导致亮氨酸匮乏,进而抑制特异肌纤维发育;补充亮氨酸可有效改善相关表型与生长水平图7)

图7.解析胎儿生长受限的细胞机制

6跨物种保守性分析

跨猪、人、鼠多器官细胞比对显示关键细胞转录保守;人源关键细胞与猪高度同源,证实妊娠调控与生长障碍机制具备高转化价值图8)

图8.跨物种细胞与基因表达高度保守

本研究构建了首个妊娠期猪全身单细胞图谱,阐明了心脏重塑、胎儿生长受限的核心机制,并证实关键通路跨物种保守,为人类妊娠相关疾病的研究与干预提供了重要依据。

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  1. CONNECT:[ UseTime:0.000580s ] mysql:host=127.0.0.1;port=3306;dbname=h_mffb;charset=utf8mb4
  2. SHOW FULL COLUMNS FROM `fenlei` [ RunTime:0.000858s ]
  3. SELECT * FROM `fenlei` WHERE `fid` = 0 [ RunTime:0.000314s ]
  4. SELECT * FROM `fenlei` WHERE `fid` = 63 [ RunTime:0.000286s ]
  5. SHOW FULL COLUMNS FROM `set` [ RunTime:0.000598s ]
  6. SELECT * FROM `set` [ RunTime:0.000238s ]
  7. SHOW FULL COLUMNS FROM `article` [ RunTime:0.000698s ]
  8. SELECT * FROM `article` WHERE `id` = 503907 LIMIT 1 [ RunTime:0.001272s ]
  9. UPDATE `article` SET `lasttime` = 1778290964 WHERE `id` = 503907 [ RunTime:0.006865s ]
  10. SELECT * FROM `fenlei` WHERE `id` = 64 LIMIT 1 [ RunTime:0.000296s ]
  11. SELECT * FROM `article` WHERE `id` < 503907 ORDER BY `id` DESC LIMIT 1 [ RunTime:0.000449s ]
  12. SELECT * FROM `article` WHERE `id` > 503907 ORDER BY `id` ASC LIMIT 1 [ RunTime:0.001518s ]
  13. SELECT * FROM `article` WHERE `id` < 503907 ORDER BY `id` DESC LIMIT 10 [ RunTime:0.009411s ]
  14. SELECT * FROM `article` WHERE `id` < 503907 ORDER BY `id` DESC LIMIT 10,10 [ RunTime:0.000954s ]
  15. SELECT * FROM `article` WHERE `id` < 503907 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.001715s ]
0.092878s