Gestational diabetes in mice induces hematopoietic memory that affects the long-term health of the offspring.
Gestational diabetes in mice induces hematopoietic memory that affects the long-term health of the offspring.
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DOI：
10.1172/jci169730
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发表时间：
2024-01-16
影响因子：
15.9
通讯作者：
Reynaud, Damien
中科院分区：
文献类型：
--
作者：
Govindarajah, Vinothini;Sakabe, Masahide;Good, Samantha;Solomon, Michael;Arasu, Ashok;Chen, Nong;Zhang, Xuan;Grimes, H. Leighton;Kendler, Ady;Xin, Mei;Reynaud, Damien
妊娠糖尿病是一种常见的妊娠并发症，与不良围产期结局相关，并增加成年后代患代谢性疾病和动脉粥样硬化的风险。造成这种延迟的病理性传播的机制仍不清楚。在小鼠模型中，我们发现糖尿病妊娠所生成年后代动脉粥样硬化的发展可能部分与造血系统的改变有关。虽然它们没有表现出任何明显的代谢紊乱，但成年后代保持了与糖尿病相关的造血特征，表明获得了持久的糖尿病造血记忆。我们发现，在妊娠期间诱导这种造血记忆依赖于晚期糖基化终产物受体（AGER）和核苷酸结合和寡聚化结构域样受体家族pyrin结构域3（NLRP 3）炎性体的活性，这导致胎盘炎症增加。在成年后代中，我们发现这种记忆与DNA甲基转移酶1（DNMT1）上调和造血祖细胞的表观遗传变化有关。总之，我们的研究结果表明，造血系统可以获得妊娠期糖尿病的持久记忆，这种记忆构成了连接妊娠期健康与成人病理的途径。糖尿病妊娠出生的成年后代获得持久的造血记忆，有助于长期的成人病理学。
Gestational diabetes is a common medical complication of pregnancy that is associated with adverse perinatal outcomes and an increased risk of metabolic diseases and atherosclerosis in adult offspring. The mechanisms responsible for this delayed pathological transmission remain unknown. In mouse models, we found that the development of atherosclerosis in adult offspring born to diabetic pregnancy can be in part linked to hematopoietic alterations. Although they do not show any gross metabolic disruptions, the adult offspring maintain hematopoietic features associated with diabetes, indicating the acquisition of a lasting diabetic hematopoietic memory. We show that the induction of this hematopoietic memory during gestation relies on the activity of the advanced glycation end product receptor (AGER) and the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which lead to increased placental inflammation. In adult offspring, we find that this memory is associated with DNA methyltransferase 1 (DNMT1) upregulation and epigenetic changes in hematopoietic progenitors. Together, our results demonstrate that the hematopoietic system can acquire a lasting memory of gestational diabetes and that this memory constitutes a pathway connecting gestational health to adult pathologies. Adult offspring born from diabetic pregnancy acquire a lasting hematopoietic memory that contributes to long-term adult pathology.
DOI：
10.1002/cyto.a.24041
发表时间：
2020-10
期刊：
Cytometry. Part A : the journal of the International Society for Analytical Cytology
影响因子：
--
作者：
Solomon M;DeLay M;Reynaud D
通讯作者：
Reynaud D
影响因子：
1.4
作者：
Govindarajah, Vinothini;Reynaud, Damien
通讯作者：
Reynaud, Damien