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解码人类骨髓造血干细胞和从胎儿到出生的祖先细胞
Xiaowei Xie1,2, Fanglin Gou3, Zhaofeng Zheng1,2
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
iScience
|August 7, 2024
概括
胎儿骨髓造血干细胞和前代细胞 (HSPCs) 在第二个三个月中期发展干细胞和分化潜力. 早期胎儿的HSPCs表现出与白血病发展相关的特征.
科学领域:
- 发展生物学 发展生物学
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
背景情况:
- 骨髓 (BM) 是怀孕20周后 (PCW) 血液形成的主要部位.
- 胎儿BM血液形成的发育轨迹及其与恶性瘤的关系尚未完全理解.
研究的目的:
- 调查胎儿BM造血干细胞和原生细胞 (HSPCs) 的单细胞转录形状.
- 阐明胎儿BM中血液形成的发育动态,从第二季度早期到新生儿阶段.
- 为了确定胎儿血液形成和白血病发生之间的潜在联系.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 用于分析BM HSPCs.
- 在三个不同的发育阶段采集样本:第二季度早期 (12-14 PCW),第二季度中期 (19-22 PCW) 和新生儿阶段.
主要成果:
- 造血干细胞和多能原始细胞 (HSC/MPP) 的干细胞在妊娠中期建立,并保持到出生.
- 经过第二个三个月的中期后,观察到对三大血统的增强分化潜力和增加的有氧代谢.
- 第二季度早期的HSPCs表现出茎度下降和干扰素信号升高,与对白血病产生更高的易感性相关.
结论:
- 胎儿血液形成在准备出生时经历了显著的动态变化,建立了茎状和分化能力.
- 早期胎儿HSPC中的特定分子特征可能会使个体易患白血病.
- 这项研究提供了对正常胎儿造血发育及其对理解白血病病变的含义的关键见解.
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