Suppr超能文献

间质细胞群体分泌的旁分泌信号调控人类肝干细胞向成体肝脏命运的扩增和分化。

Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates.

机构信息

Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.

出版信息

Hepatology. 2010 Oct;52(4):1443-54. doi: 10.1002/hep.23829.

Abstract

UNLABELLED

The differentiation of embryonic or determined stem cell populations into adult liver fates under known conditions yields cells with some adult-specific genes but not others, aberrant regulation of one or more genes, and variations in the results from experiment to experiment. We tested the hypothesis that sets of signals produced by freshly isolated, lineage-dependent mesenchymal cell populations would yield greater efficiency and reproducibility in driving the differentiation of human hepatic stem cells (hHpSCs) into adult liver fates. The subpopulations of liver-derived mesenchymal cells, purified by immunoselection technologies, included (1) angioblasts, (2) mature endothelia, (3) hepatic stellate cell precursors, (4) mature stellate cells (pericytes), and (5) myofibroblasts. Freshly immunoselected cells of each of these subpopulations were established in primary cultures under wholly defined (serum-free) conditions that we developed for short-term cultures and were used as feeders with hHpSCs. Feeders of angioblasts yielded self-replication, stellate cell precursors caused lineage restriction to hepatoblasts, mature endothelia produced differentiation into hepatocytes, and mature stellate cells and/or myofibroblasts resulted in differentiation into cholangiocytes. Paracrine signals produced by the different feeders were identified by biochemical, immunohistochemical, and quantitative reverse-transcription polymerase chain reaction analyses, and then those signals were used to replace the feeders in monolayer and three-dimensional cultures to elicit the desired biological responses from hHpSCs. The defined paracrine signals were proved to be able to yield reproducible responses from hHpSCs and to permit differentiation into fully mature and functional parenchymal cells.

CONCLUSION

Paracrine signals from defined mesenchymal cell populations are important for the regulation of stem cell populations into specific adult fates; this finding is important for basic and clinical research as well as industrial investigations.

摘要

未加标签

在已知条件下,胚胎或确定的干细胞群体分化为成人肝脏命运,产生具有一些成人特异性基因但不具有其他基因的细胞,一个或多个基因的异常调节,以及实验之间结果的变化。我们测试了一个假设,即新鲜分离的、依赖谱系的间充质细胞群体产生的信号集将在驱动人类肝干细胞(hHpSCs)分化为成人肝脏命运方面产生更高的效率和重现性。通过免疫选择技术纯化的肝来源的间充质细胞亚群包括(1)成血管细胞,(2)成熟内皮细胞,(3)肝星状细胞前体,(4)成熟星状细胞(周细胞)和(5)肌成纤维细胞。这些亚群中的每一个的新鲜免疫选择细胞都在我们为短期培养开发的完全定义(无血清)条件下建立了原代培养,并用作 hHpSCs 的饲养细胞。成血管细胞的饲养细胞产生自我复制,星状细胞前体导致肝母细胞的谱系限制,成熟内皮细胞产生向肝细胞的分化,而成熟星状细胞和/或肌成纤维细胞导致向胆管细胞的分化。通过生化、免疫组织化学和定量逆转录聚合酶链反应分析鉴定不同饲养细胞产生的旁分泌信号,然后将这些信号用于单层和三维培养中替代饲养细胞,以从 hHpSCs 中引发所需的生物学反应。已证明定义的旁分泌信号能够从 hHpSCs 中产生可重现的反应,并允许分化为完全成熟和功能的实质细胞。

结论

来自定义的间充质细胞群体的旁分泌信号对于将干细胞群体调节为特定的成人命运是重要的;这一发现对于基础和临床研究以及工业研究都很重要。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验