Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics.

Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics.
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DOI:
10.1016/j.devcel.2022.01.004
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发表时间:
2022-02-07
期刊:
影响因子:
11.8
通讯作者:
Feng GS
Feng GS
中科院分区:
生物学1区
文献类型:
--
作者:
Liang Y;Kaneko K;Xin B;Lee J;Sun X;Zhang K;Feng GS

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肝脏是机体的主要代谢器官,其出生后的发育和成熟尚未得到充分的了解。我们分析了52,834个单细胞转录组,并在出生后第1、3、7、21和56天的小鼠肝脏中鉴定了31种细胞类型或状态。我们观察到意外高水平的肝细胞异质性在发展中的肝脏和分区的代谢功能从中央到门静脉周围肝细胞,这是精心策划的发展窦状内皮细胞,星状细胞和枯否细胞的渐进式建设。轨迹和基因调控分析捕获36个转录因子,包括昼夜节律调节器Bhlhe 40,在编程肝脏发育。值得注意的是,我们确定了一组特殊的巨噬细胞富集在第7天的巨噬细胞和内皮细胞的混合表型,这可能会调节窦建设和调节性T细胞功能。这项研究提供了一个全面的图谱,涵盖了所有肝细胞类型,有助于进一步解剖肝脏发育,代谢和疾病。Liang等人以单细胞分辨率展示了从新生儿到成年小鼠肝脏发育的图谱。它们证明了肝细胞与内皮细胞、星状细胞和枯否细胞的功能成熟以及巨噬细胞群的短暂出现。
The postnatal development and maturation of liver, the major metabolic organ, are inadequately understood. We have analyzed 52,834 single cell transcriptomes and identify 31 cell types or states in mouse livers at postnatal day 1, 3, 7, 21 and 56. We observe unexpectedly high levels of hepatocyte heterogeneity in the developing liver and progressive construction of the zonated metabolic functions from pericentral to periportal hepatocytes, which is orchestrated with development of sinusoid endothelial, stellate and Kupffer cells. Trajectory and gene regulatory analyses capture 36 transcription factors, including a circadian regulator Bhlhe40, in programming liver development. Remarkably, we identify a special group of macrophages enriched at day 7 with a hybrid phenotype of macrophages and endothelial cells, which may regulate sinusoidal construction and Treg cell function. This study provides a comprehensive atlas that covers all hepatic cell types instrumental for further dissection of liver development, metabolism and disease. Liang et al. present an atlas of mouse liver development at single cell resolution from newborn to adult. They demonstrate functional maturation of hepatocytes in concert with endothelial, stellate and Kupffer cells and transient emergence of a macrophage group.
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