Hedgehog signaling maintains resident hepatic progenitors throughout life
Hedgehog signaling maintains resident hepatic progenitors throughout life
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DOI：
10.1152/ajpgi.00456.2005
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发表时间：
2006-05-01
影响因子：
4.5
通讯作者：
Diehl, AM
中科院分区：
文献类型：
--
作者：
Sicklick, JK;Li, YX;Diehl, AM
Hedgehog信号通过其受体Patched激活基因的转录，包括Patched，调节各种祖细胞的命运。虽然Hedgehog信号传导是内胚层定型和肝发生所必需的，但由于成熟的肝上皮细胞缺乏Hedgehog信号传导，因此未考虑其调节成人肝脏周转的可能性。在此，我们表明该途径对于维持肝脏祖细胞在一生中至关重要。已在内胚层谱系限制的鼠胚胎干细胞以及胎儿和成年Ptc-lacZ小鼠的肝脏中鉴定出补丁表达细胞。成人来源的鼠肝祖细胞系表达Patched和Hedgehog应答细胞，存在于胎儿和成人肝脏的干细胞区室中。在这两个物种中，操纵Hedgehog活性影响肝祖细胞存活。因此，Hedgehog信号在肝祖细胞中从胎儿发育到成年都是保守的，可能是肝损伤患者的新治疗靶点。
Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stem cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage.