【讨论】干细胞的诱导分化

jinyuwei

希望大家在此相互交流，相互学习，共同提高
* @. P: c  N% e; `5 S1、自己或者实验室对干细胞诱导分化的研究
; {' A6 C3 @: E. P* X" m; k2、干细胞的诱导分化的最新进展 3 ?# T" m$ V7 E! d( f2 w
3、调控分化的相关基因和蛋白及相关的网络调控
1 O1 N& j7 J8 q. H) f* J) H4、相关的研究方法

jinyuwei

呵呵。我也是搞干细胞的。
2 k6 h( n2 z6 C我也想问一个问题，是细胞因子对干细胞的分化起重要作用呢，还是细胞间接触更为重要呢，或者两者兼而有之。6 d  H* n! s" k2 ?0 `/ O
我想既然微环境的影响很重要，是不是细胞接触比较重要呢？

jinyuwei

一点浅见：
( a0 E. Q1 v4 C% d细胞分化受到细胞间相互作用和环境因素的影响！生物个体的生长发育离不开环境，环境中的物理、化学、生物因素往往以提供信号的方式影响集体的细胞分化；细胞因子对细胞分化的影响可以看作是远距离细胞间的相互作用。前几年干细胞分化中细胞因子研究的比较多，近几年微环境（stem cell niche）研究的比较多了，原因我想是这样的：细胞因子的作用相对于微环境的影响来说是比较简单的！随着研究的进一步深入，niche 的研究可能越来越热！

jinyuwei

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6 i/ t1 n$ p4 L* `* N* U1 J5 \9 R 其实神经干细胞的分化是一个复杂的过程，有物理因素和化学因数参与。所谓的局部微环境，现在主要指局部的细胞因子，其实仅仅局限于化学因素，其实如何影响或者激活、启动细胞的内在基因的表达才是最关键的！！！所谓局部微环境其实也是一种模糊的称呼，随着科研的进步，一定会揭示局部起重要作用的细胞因子。我相信一定存在一种如同糖代谢通路似的机制，在分化调控中，现在已经有几条通路，但还有待进一步发现与总结。

jinyuwei

我觉得因子和环境都重要

jinyuwei

微环境中细胞因子的作用当然是很重要的，但不是唯一的，细胞间的相互作用也是不可忽视的『当然细胞间相互作用的机制可能是分泌细胞因子（旁分泌方式）』。

jinyuwei

细胞之间通过什么机制来作用呢？  M" \$ }0 o, g: B
1、通过分泌细胞因子来实现相互作用，这是最为常见的作用方式，可以包括通过血液运输扩散到全身，形成全身效应，也可以通过旁分泌，达到某个区域局部细胞的相互调节，可以相互促进也可以相互抑制+ ^; f# A# `* _- }4 R
2、可以通过接触相互作用，少突胶质细胞的髓鞘可以抑制神经元新的突起的形成就是一个例子
, _/ `9 D6 q0 Y' [3、可以通过信使分子，作用于细胞核内，影响细胞的基因表达和调空" n) \( N7 A) C
4、局部微环境的基质成分、纤维也可以发挥一些物理作用，以及导向作用。放射状胶质细胞在神经干系报分化的过程中发挥重要的作用。

jinyuwei

最近在学习关于人类成体干细胞的在不同诱导条件下的分化问题/ g) x+ j# M. i7 y! Y
主要是诱导成体干细胞想骨\软骨\神经\肌肉等多向分化的调控问题
& Y8 l% |+ o2 e5 V有兴趣的高手可以一起好好切磋一下经验哦

jinyuwei

干细胞的诱导分化是热点也是难点/ k' B' ^. W. g
目前研究的方向有以下几个方面：
4 G, ]5 t- j. B# P7 w, [$ M$ |9 |: b" Z6 \1、继续寻找相关的基因和细胞因子，通过基因封闭和基因敲除- c: u- s; \9 S. h+ k
2、深入研究已知基因的功能和作用通路，包括调空途径和上下游作用环节  ~4 |/ G$ [6 a& t. p
3、网络调空，因为作为最为复杂和精细的神经系统的发育，有许多的基因和细胞因子参与

jinyuwei

我看到的一点文献（整理过），与大家分享。) `" i" ?# C+ S% P) Z$ E% n
In addition to stem cells for hematopoietic cells, bone marrow contains stem-like cells that are precursors of non-hematopoietic cells and can be cultivated in vitro. They were initially referred to as plastic adherent cells or colony-forming-unit fibroblasts and recently as mesenchymal stem cells or marrow stromal cells. Marrow stromal cells are connective tissue elements that provide structural and functional support for hemopoiesis, but they are now recognized as progenitor cells capable of differentiating into mesenchymal tissues of bone, cartilage, fat, muscle and other connective tissue. In addition to these tissues, transdifferentiation of MSCs into the neuronal lineage such as astrocytes and neurons has been reported. Therefore, they are an interesting target for use in neural transplantation and regeneration. This section demonstrates that MSCs can be induced to differentiate into cells with Schwann cell characteristics that are capable of eliciting regeneration of the sciatic and optic nerves. MSCs were obtained from adult rat (Wistar strain) bone marrow, and were subcultured four times. They were then treated with b-mercaptoethanol (BME) followed by retinoic acid (RA) and cultured in the presence of FSK, bFGF, PDGF and heregulin (HRG). Such differentiated MSCs were morphologically different from the original undifferentiated MSCs and resembled primary cultured Schwann cells." V( v7 a7 D8 }2 y4 m  i. U0 t
As noted above, FSK increases the level of cAMP, which increases mitogenic responses at an early time perhaps by stimulating the expression of growth factor receptors. Thus, FSK together with bFGF, PDGF and HRG could have a synergistic effect in enhancing these factors to MSCs. Although further investigations on the mechanism of the MSC differentiation are required, the sequential administration of the reagents used in this experiment seems cumulative for the differentiation of MSCs to express the Schwann cell phenotype because an omission of any one of the above factors resulted in an incomplete differentiation of MSCs regarding morphology and immunoreactivity to Schwann cell markers.