Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration

Zhang, Junren; Zhou, Yang; Li, Shuang; Mo, Dashuang; Ma, Jianlong; Ni, Rui; Yang, Qifen; He, Jianbo; Luo, Lingfei

doi:10.1016/j.celrep.2022.110596

Cited by 11 publications

(11 citation statements)

References 86 publications

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“…It was revealed using the zebrafish model that Notch signaling, 96 bromodomain and extraterminal (BET) proteins, 98 Dnmt1, 99 and mTORC1 100 regulate the first step of the conversion process, BEC-to-LPC dedifferentiation. It was also revealed that the second step, LPC proliferation, is positively regulated by BET proteins, 98 Tel2, 101 and Stat3 102 and negatively regulated by Notch 91 and FXR 103 signaling. Specifically, FXR activation did not only suppress LPC proliferation but also induced its death.…”

Section: Bec-to-hepatocyte Conversion In Animal Modelsmentioning

confidence: 99%

“…103 Given the correlation between LPC number and the severity of human liver diseases 21 104 and the potential of regenerative therapy to promote LPC-to-hepatocyte differentiation in the diseased livers, the third step, LPC-to-hepatocyte differentiation, was more extensively investigated using the zebrafish model than the other steps. It was revealed that BMP signaling 105 and Tel2 101 positively regulate the third step through Tbx2b and Hhex, respectively, and that Notch signaling negatively regulates the step. 91 96 Epigenetic regulators, Hdac1 106 and Dnmt1, 99 also positively control LPC-to-hepatocyte differentiation by repressing sox9b and tp53 expression, respectively.…”

Section: Bec-to-hepatocyte Conversion In Animal Modelsmentioning

confidence: 99%

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Update on Hepatobiliary Plasticity

et al. 2023

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The liver field has been debating for decades the contribution of the plasticity of the two epithelial compartments in the liver, hepatocytes and biliary epithelial cells (BECs), to derive each other as a repair mechanism. The hepatobiliary plasticity has been first observed in diseased human livers by the presence of biphenotypic cells expressing hepatocyte and BEC markers within bile ducts and regenerative nodules or budding from strings of proliferative BECs in septa. These observations are not surprising as hepatocytes and BECs derive from a common fetal progenitor, the hepatoblast, and, as such, they are expected to compensate for each other's loss in adults. To investigate the cell origin of regenerated cell compartments and associated molecular mechanisms, numerous murine and zebrafish models with ability to trace cell fates have been extensively developed. This short review summarizes the clinical and preclinical studies illustrating the hepatobiliary plasticity and its potential therapeutic application.

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Section: Bec-to-hepatocyte Conversion In Animal Modelsmentioning

confidence: 99%

Section: Bec-to-hepatocyte Conversion In Animal Modelsmentioning

confidence: 99%

Update on Hepatobiliary Plasticity

et al. 2023

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“…ENU mutagenesis and positional cloning of the lvv mutant ENU mutagenesis was carried out as previously described 56 for mutations affecting liver regeneration. Briefly, the adult male zebrafish of Tg(lfabp:DenNTR) cq1 were treated with 3.5 mM ENU for 1 h at weekly intervals and repeated for six times.…”

Section: Zebrafish Strainsmentioning

confidence: 99%

“…Heterozygous lvv fish were crossed with the polymorphic line SJD to generate the mapping population. Positional cloning was carried out as previously described [56][57][58] . The mutation was mapped to chromosome 16 by bulk segregation analysis with simple sequence length polymorphism (SSLP) markers Z6021 and Fig.…”

Section: Zebrafish Strainsmentioning

confidence: 99%

The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway

Song

Liu

et al. 2023

npj Regen Med

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When the proliferation of residual hepatocytes is prohibited, biliary epithelial cells (BECs) transdifferentiate into nascent hepatocytes to accomplish liver regeneration. Despite significant interest in transdifferentiation, little is known about the maintenance of nascent hepatocytes in post-injured environments. Here, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a mutant containing a nonsense mutation in the gene nibrin (nbn), which encodes a component of the Mre11-Rad50-Nbn (MRN) complex that activates DNA damage response (DDR). The regenerated hepatocytes cannot be maintained and exhibit apoptosis in the mutant. Mechanistically, the nbn mutation results in the abrogation of ATR-Chk1 signaling and accumulations of DNA damage in nascent hepatocytes, which eventually induces p53-mediated apoptosis. Furthermore, loss of rad50 or mre11a shows similar phenotypes. This study reveals that the activation of DDR by the MRN complex is essential for the survival of BEC-derived hepatocytes, addressing how to maintain nascent hepatocytes in the post-injured environments.

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“…Liver has a remarkable regenerative capacity when it is damaged by injury or surgical resection [ 1 , 2 , 3 ]. 2/3 PH, also known as 70% PH, refers to the removal of the middle and left lobes of liver that account for 70% of the total liver [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of miR-125a-5p Inhibits Hepatocyte Proliferation through the STAT3 Regulation In Vivo and In Vitro

Zhao

Wang

Qin

et al. 2022

IJMS

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microRNAs (miRNAs) are critically involved in liver regeneration (LR). miR-125a-5p (miR-125a) is a tumor-suppressing miRNA, but its role in LR has not been studied. Our previous studies have proved that miR-125a was related to LR at the initiation phase, while the mechanism hepatocyte proliferation triggered by miR-125a in LR has been rarely evaluated. Herein, we mainly studied the molecular mechanism of miR-125a in triggering hepatocyte proliferation and the proliferation stage of LR. Firstly, a striking reduction of miR-125a was found at 24 h as well as 30 h following partial hepatectomy (PH) in rat liver tissue by miRNAs expression profiles as well as qRT-PCR analysis. Furthermore, in vitro, upregulation of miR-125a decreased proliferation as well as G1/S conversion, which promoted hepatocytes apoptosis. STAT3 was the target of miR-125a. In vivo, upregulation of miR-125a by tail vein injection of agomir inhibited LR index. Upregulation of miR-125a inhibited LR index and hepatocytes proliferation by STAT3/p-STAT3/JUN/BCL2 axis. In summary, these current discoveries indicated that miR-125a inhibited hepatocytes proliferation as well as LR by targeting STAT3 and via acting on the STAT3/p-STAT3/JUN/BCL2 axis.

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Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration

Cited by 11 publications

References 86 publications

Update on Hepatobiliary Plasticity

Update on Hepatobiliary Plasticity

The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway

Overexpression of miR-125a-5p Inhibits Hepatocyte Proliferation through the STAT3 Regulation In Vivo and In Vitro

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