Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
Stem Cells. 2022 Aug 25;40(8):751-762. doi: 10.1093/stmcls/sxac034.
Pluripotent stem cells (PSCs) have unlimited self-renewal and multifunctional development potential in vitro. Porcine PSCs are highly desirable due to the conserved characteristics between pigs and humans. Extended PSCs (EPSCs) are additionally capable of differentiating into embryonic (Em) and extraembryonic (E×Em) parts. Here, we employed the LCDM culture system (consisting of human LIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride), which can establish EPSCs from humans and mice, to derive and maintain stable porcine PSCs (pLCDM) from in vivo blastocysts. Transcriptome analysis revealed the unique molecular characteristics of pLCDMs compared with early-stage embryos. Meanwhile, the parallels and differences in the transcriptome features among pLCDMs, human EPSCs, and mouse EPSCs were carefully analyzed and evaluated. Most noteworthy, the trophoblast lineage differentiation tendency of pLCDMs was clarified by inducing trophoblast-like cells and trophoblast stem cells (TSCs) in vitro. Further research found that 2 of the small molecules in LCDM culture system, (S)-(+)-dimethindene maleate (DiM) and minocycline hydrochloride (MiH), probably play a crucial role in promoting trophoblast lineage differentiation potential of pLCDMs.
多能干细胞（PSCs）在体外具有无限自我更新和多功能发育的潜力。由于猪和人类之间具有保守的特征，因此猪 PSCs 是非常理想的。扩展 PSCs（EPSCs）还能够分化为胚胎（Em）和胚胎外（E×Em）部分。在这里，我们采用了 LCDM 培养系统（包含人 LIF、CHIR99021、（S）-（+）-二甲茚满马来酸盐和盐酸米诺环素），该系统能够从人和小鼠中建立 EPSCs，从体内囊胚中分离和维持稳定的猪 PSCs（pLCDM）。转录组分析揭示了 pLCDM 与早期胚胎相比具有独特的分子特征。同时，仔细分析和评估了 pLCDM、人 EPSCs 和鼠 EPSCs 之间在转录组特征上的相似性和差异。最值得注意的是，通过体外诱导滋养层样细胞和滋养层干细胞（TSCs），阐明了 pLCDM 的滋养层谱系分化倾向。进一步的研究发现，LCDM 培养系统中的 2 种小分子，（S）-（+）-二甲茚满马来酸盐（DiM）和盐酸米诺环素（MiH），可能在促进 pLCDM 的滋养层谱系分化潜力方面发挥着关键作用。
