Prenatal inflammation perturbs murine fetal hematopoietic development and causes persistent changes to postnatal immunity.
Prenatal inflammation perturbs murine fetal hematopoietic development and causes persistent changes to postnatal immunity.
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DOI：
10.1016/j.celrep.2022.111677
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发表时间：
2022-11-22
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
成体造血干细胞和祖细胞（HSPC）直接对炎症和感染作出反应，导致静止、动员和分化的急性和持续变化。在这里，我们表明，小鼠胎儿HSPCs响应产前炎症在子宫内，胎儿的反应形状出生后造血和免疫细胞功能。异质性胎儿HSPCs表现出不同的反应，母体免疫激活（MIA），包括变化的静止，扩张，和谱系偏向的输出。胎儿HSPC对MIA的单细胞转录组学分析揭示了离散的、瞬时的造血干细胞（HSC）群体中炎性基因谱的特异性上调，所述造血干细胞（HSC）群体传播淋巴偏向的祖细胞的扩增。除了胎儿发育，MIA导致胎儿淋巴细胞偏向的祖细胞出生后的不适当的扩张和持久性，伴随着胎儿来源的先天性淋巴细胞的细胞结构和高反应性。我们的研究表明，子宫内的炎症如何通过重塑胎儿HSC的建立来指导胎儿源性免疫细胞的输出和功能。López等人报告，产前炎症在胎儿发育期间诱导淋巴偏向的造血反应，由瞬时淋巴偏向的造血干细胞激活驱动。出生后，这导致骨髓祖细胞室的持续变化，并伴随着胎儿衍生的先天性淋巴细胞样后代的扩增和过度活化。
Adult hematopoietic stem and progenitor cells (HSPCs) respond directly to inflammation and infection, causing both acute and persistent changes to quiescence, mobilization, and differentiation. Here we show that murine fetal HSPCs respond to prenatal inflammation in utero and that the fetal response shapes postnatal hematopoiesis and immune cell function. Heterogeneous fetal HSPCs show divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and lineage-biased output. Single-cell transcriptomic analysis of fetal HSPCs in response to MIA reveals specific upregulation of inflammatory gene profiles in discrete, transient hematopoietic stem cell (HSC) populations that propagate expansion of lymphoid-biased progenitors. Beyond fetal development, MIA causes the inappropriate expansion and persistence of fetal lymphoid-biased progenitors postnatally, concomitant with increased cellularity and hyperresponsiveness of fetal-derived innate-like lymphocytes. Our investigation demonstrates how inflammation in utero can direct the output and function of fetal-derived immune cells by reshaping fetal HSC establishment. López et al. report that prenatal inflammation induces a lymphoid-biased hematopoietic response during fetal development, driven by the activation of a transient, lymphoid-biased hematopoietic stem cell. Postnatally, this results in sustained changes to the bone marrow progenitor compartment and accompanying expansion and hyperactivation of fetal-derived innate-like lymphocyte progeny.
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影响因子：
5.9
作者：
Gazit, Roi;Garrison, Brian S.;Rao, Tata Nageswara;Shay, Tal;Costello, James;Ericson, Jeff;Kim, Francis;Collins, James J.;Regev, Aviv;Wagers, Amy J.;Rossi, Derrick J.
通讯作者：
Rossi, Derrick J.
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
DOI：
10.1084/jem.20072168
发表时间：
2008-05-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Benz C;Martins VC;Radtke F;Bleul CC
通讯作者：
Bleul CC
影响因子：
6.7
作者：
Furusawa J;Mizoguchi I;Chiba Y;Hisada M;Kobayashi F;Yoshida H;Nakae S;Tsuchida A;Matsumoto T;Ema H;Mizuguchi J;Yoshimoto T
通讯作者：
Yoshimoto T
影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer