Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration.

Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration.
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Mfsd2a 肝细胞在损伤和再生过程中重新填充肝脏

DOI:
10.1038/ncomms13369
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发表时间:
2016-11-18
影响因子:
16.6
通讯作者:
Zhou, Bin
Zhou, Bin
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pu, Wenjuan;Zhang, Hui;Huang, Xiuzhen;Tian, Xueying;He, Lingjuan;Wang, Yue;Zhang, Libo;Liu, Qiaozhen;Li, Yan;Li, Yi;Zhao, Huan;Liu, Kuo;Lu, Jie;Zhou, Yingqun;Huang, Pengyu;Nie, Yu;Yan, Yan;Hui, Lijian;Lui, Kathy O.;Zhou, Bin

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肝细胞在功能上是异质的,并根据其代谢分区分为两个不同的群体:门静脉周围和中央周围肝细胞。在肝损伤和再生过程中,这两个不同群体的细胞动力学在很大程度上仍然难以捉摸。在这里,我们表明,主要促进剂超家族域包含2a(Mfsd2a),以前已知的维持血脑屏障功能,是一个门静脉周围的分区标记。通过对Mfsd2a+门静脉周围肝细胞的遗传谱系追踪,我们发现在肝脏稳态期间Mfsd2a+群体减少。然而,部分肝切除术诱导的肝再生显著刺激Mfsd2a+门静脉周围肝细胞的扩增。类似地,在慢性肝损伤期间,Mfsd2a+肝细胞群体扩增并完全取代整个肝脏中的中心周围肝细胞群体。损伤恢复后,成年肝脏通过将Mfsd2a+衍生的肝细胞重编程为中央周围肝细胞来重建代谢分区。损伤过程中整个区域替换的证据增加了我们对肝脏生物学和疾病的理解。
Hepatocytes are functionally heterogeneous and are divided into two distinct populations based on their metabolic zonation: the periportal and pericentral hepatocytes. During liver injury and regeneration, the cellular dynamics of these two distinct populations remain largely elusive. Here we show that major facilitator super family domain containing 2a (Mfsd2a), previously known to maintain blood–brain barrier function, is a periportal zonation marker. By genetic lineage tracing of Mfsd2a+ periportal hepatocytes, we show that Mfsd2a+ population decreases during liver homeostasis. Nevertheless, liver regeneration induced by partial hepatectomy significantly stimulates expansion of the Mfsd2a+ periportal hepatocytes. Similarly, during chronic liver injury, the Mfsd2a+ hepatocyte population expands and completely replaces the pericentral hepatocyte population throughout the whole liver. After injury recovery, the adult liver re-establishes the metabolic zonation by reprogramming the Mfsd2a+-derived hepatocytes into pericentral hepatocytes. The evidence of entire zonation replacement during injury increases our understanding of liver biology and disease.
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发表时间: 2014-05-22
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影响因子: 64.8
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