Induced hepatic stem cells are suitable for human hepatocyte production.

Induced hepatic stem cells are suitable for human hepatocyte production.
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诱导的肝干细胞适用于人肝细胞的产生。

DOI:
10.1016/j.isci.2022.105052
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发表时间:
2022-10-21
期刊:
影响因子:
5.8
通讯作者:
Noguchi, Hirofumi
Noguchi, Hirofumi
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Nakashima, Yoshiki;Miyagi-Shiohira, Chika;Saitoh, Issei;Watanabe, Masami;Matsushita, Masayuki;Tsukahara, Masayoshi;Noguchi, Hirofumi

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用表达OCT 3/4、SOX 2、KLF 4和C-MYC的仙台病毒载体(SeV)转染人肝细胞以产生肝细胞衍生的诱导多能干细胞(iPSC)。检查48个建立的肝细胞衍生的iPSC样集落中未分化标志物(第19-21代)和肝细胞特异性标志物(HSM)(第0-20代)的信使RNA(mRNA)表达。在48个克隆中,10个克隆在0-20代持续表达HNF 1 β和HNF 4 α。表达HSM的集落(iTS-L细胞:来自肝脏的诱导组织特异性干细胞)在微阵列和甲基化分析中显示出与成纤维细胞来源的iPSC(品系:201 B7)不同的趋势。iTS-L细胞在小鼠中形成畸胎瘤的可能性低于iPSC(He)。iTS-L细胞比iPSC(He)或iPSC(201 B7)更有效地分化成肝细胞样细胞。这些数据表明表达0 CT 3/4、S 0X 2、KLF 4和C-MYC的SeV诱导iPSC和iTS-L细胞的产生。iTS细胞具有自我更新和多能性iTS细胞表达组织特异性标志物iTS-L细胞比iPSC更不容易形成畸胎瘤人类;生物科学;细胞生物学;干细胞研究;发育生物学
Human hepatocytes were transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (HSMs) (passage 0-20) in 48 established hepatocyte-derived iPSC-like colonies was examined. Among the 48 clones, 10 clones continuously expressed HSM mRNA (HNF1β and HNF4α) in passage 0-20. The colonies which expressed HSMs (iTS-L cells: induced tissue-specific stem cells from liver) showed a different tendency in microarray and methylation analyses to fibroblast-derived iPSCs (strain: 201B7). iTS-L cells were less likely to form teratomas in mice than iPSCs (He). The iTS-L cells were differentiated into hepatocyte-like cells more efficiently than iPSCs (He) or iPSCs (201B7). These data suggest that SeV expressing OCT3/4, SOX2, KLF4, and C-MYC induce the generation of iPSCs and iTS-L cells. iTS cells have self-renewal and multipotency iTS cells express tissue-specific markers iTS-L cells are less prone to teratoma formation than iPSCs Human; Biological sciences; Cell biology; Stem cells research; Developmental biology
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