paulin98122

MSC具有可塑性，可以向各个胚层细胞分化，了解具体的机制对MSC的临床应用具有重要意义。抛砖引玉，这次讨论主要是关于MSC向成骨细胞、软骨细胞、脂肪细胞、肝细胞、神经细胞分化的通路及机制。这些分化与BMP, TGF-β, Wnt, 及Indian hedgehog (Ihh)信号有关。

影响干细胞分化的因素很多

paulin98122

1.Role of BMP signaling in osteoblastogenesis and chondrogenesis




[ 本帖最后由 paulin98122 于 2008-7-20 22:53 编辑 ]

paulin98122

2. Wnt signaling and bone

Fig. 3. Control of the Wnt signaling pathway. Wnt elicits three signaling pathways:  β-catenin/Lef, PCP (planer cell polarity), and Ca2+. DKK and sFRP func-tion as antagonists for Wnt signaling

paulin98122

3.Role of Ihh signaling in chondrocytes and osteoblasts

paulin98122

4. Determination between osteoblasts and adipocytes


[ 本帖最后由 paulin98122 于 2008-7-21 09:12 编辑 ]

paulin98122

5. A role of Wnt/beta-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells
Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1089-98.

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to be an excellent source of cells for transplantation. In addition, the stem cell plasticity of human UCBMSCs, which can transdifferentiate into hepatocytes, has been reported. However, the mechanisms involved remain to be clarified. To identify the genes and/or signals that are important in specifying the hepatic fate of human UCBMSCs, we analyzed gene expression profiles during the hepatic differentiation of UCBMSCs with human telomerase reverse transcriptase, UCBMSCs immortalized by infection with a retrovirus carrying telomerase reverse transcriptase, but whose differentiation potential remains unchanged. Efficient differentiation was induced by 5-azacytidine (5-aza)/hepatocyte growth factor (HGF)/oncostatin M (OSM)/fibroblast growth factor 2 (FGF2) treatment in terms of function as well as protein expression: 2.5-fold increase in albumin, 4-fold increase in CCAAT enhancer-binding protein alpha, 1.5-fold increase in cytochrome p450 1A1/2, and 8-fold increase in periodic acid-Schiff staining. Consequently, we found that the expression of Wnt/beta-catenin-related genes downregulated, and the translocation of beta-catenin was observed along the cell membrane and in the cytoplasm, although some beta-catenin was still in the nucleus. Downregulation of Wnt/beta-catenin signals in the cells by Fz8-small interference RNA treatment, which was analyzed with a Tcf4 promoter-luciferase assay, resulted in similar hepatic differentiation to that observed with 5-azacytidine/HGF/OSM/FGF2. In addition, the subcellular distribution of beta-catenin was similar to that of cells treated with 5-azacytidine/HGF/OSM/FGF2. In conclusion, the suppression of Wnt/beta-catenin signaling induced the hepatic differentiation of UCBMSCs, suggesting that Wnt/beta-catenin signals play an important role in the hepatic fate specification of human UCBMSCs. Wnt/beta-catenin的下调促进UCBMSCs的肝分化
全文

[ 本帖最后由 paulin98122 于 2008-7-21 09:11 编辑 ]

paulin98122

6. 干细胞向神经细胞的分化有很多信号通路参与，包括： hedgehog pathway, Wnt signaling, Notch signaling, BMP signaling, MAPKE pathway

vnewjay

请教楼主一个问题：

不同组织来源的MSC向一定的方向分化是否都经相同的通路调节呢？

vnewjay

不同组织来源的MSC的表观遗传似乎并不相同！

所以，是否通用调节通路呢？

hackstem

总版主，这个有没有文献做过呀？

zhousjplasur

通路信号问题个人感觉似乎是一个既不能回避但又较难理清的一个问题。单单说研究出MSC中有某某通路信号并不能说明问题。应该具体深入到某一通路侧重于对differentation的某一方面才能更具意义。

paulin98122

“不同组织来源的MSC的表观遗传似乎并不相同！”

不同物种不同组织来源的MSC的通路是否通用还没有人做过，应该不能通用

paulin98122

“单单说研究出MSC中有某某通路信号并不能说明问题。应该具体深入到某一通路侧重于对differentation的某一方面才能更具意义。”
同意！ ，比如Notch通路在MSC心肌分化中的应用

vnewjay

问题的关键是MSC起始到底处于那种状态——发育早期？发育中？发育晚期？以逆分化的形式存在？。。。。。。。。。。。因为，不同的存在状态则决定着细胞内的分子机制！

还有一个问题，MSC存在的意义？为什么体内大量存留这样的细胞？仅仅为了当“替补”吗？还是扮演着其他的“角色”？

在原代MSC这样一群混杂的细胞中，即使经过流式和磁珠分选，依然不能达到完全的一致，何况表面的标志就还没有完全定论，所以，个人所见，内在的分化机制对于MSC而言，可能没有一个固定的答案！

icerwyj

有一个疑问，不同组织来源的MSC，分化能力是否相同？不同年龄阶段来源的MSC分化能力是否相同？哪位大侠有相关文献？可提供一下。邮箱icerwyj@163.com
谢谢先