【活动】总结干细胞发育和分化信号通路

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【活动】总结干细胞发育和分化信号通路 [精华]

franca2008

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2008-03-19 20:13

打算总结出与干细胞有关的发育或者分化的图片，简短的列表，目的是为了简明易懂为初学者做一个知识的积累，也为临床的朋友提供和干细胞，癌症增殖或者分化相结合的一些内容，对图片的评论或者对biocarta图片的理解甚至是新知识点的增加，还有原创图片都很好，等时间长了，总结一下，留给大家做一份资源。参与者只要内容相关都有加分。

stemcells edited on 2008-03-23 22:10

• 【讨论】反复胸闷、气短10个月余,加重伴不能平卧4个月

franca2008

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2008-03-19 20:13

先贴上一个，抛砖引玉

• 【转载】被SCI收录的《中国神经再生研究（英文版）》(Neural Regeneration Research NRR)杂志

stemcells

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2008-03-23 20:56

强烈支持版主的这个活动，望大家积极参与。

欢迎来干细胞与再生医学版交流讨论！ http://www.zhihuiyixue.com/bbs/post/page?bid=104&sty=1&age=30

• 【转载】支持尽快修改现行《中华人民共和国执业医师法》的来签名

stemcells

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2008-03-23 21:13

wnt通路
Wnt family members are secreted glycoproteins who bind to cell surface receptors such as Frizzled. Wnt members can play a role in the expression of many genes by interacting with multiple disparate signaling pathways. Shown is the Wnt/beta-catenin pathway.

欢迎来干细胞与再生医学版交流讨论！ http://www.zhihuiyixue.com/bbs/post/page?bid=104&sty=1&age=30

• 【共享】道少斋医话.

stemcells

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2008-03-23 21:20

角质形成细胞的分化：
The epidermis, which provides a protective barrier that undergoes a constant renewal, is a multi-layered tissue with the proliferating cells located in the basal layer. As cells leave the basal layer the underog significant differentiation, biochemical and morphological remodeling. The final differentiation results in the formation of corneocytes. In vitro keratinocytes mimic this process. Several genes mark keratinocyte specific differentiation. Among the most frequently tracked markers are Transglutaminase, Cystatin and Involucrin.
The keratinocyte differentiation studies have identified and provided significant detail regarding the involvement of three of the 4 major MAP kinase pathways (see MAPKinase Signaling Pathway ) from several diverse stimuli such as EGF, FAS, TNF and Calicium influx. The p38 cascade is represented twice since both p38alpha (p38) and p38delta (MAPK13) are involved. The keratinocyte differentiation cascased also provide for detailed study of the functions of individual PKC isoforms. It is interesting to note the contrasting functions of the PKC isoforms in this process. In recent studies it has been determined that the cPKC (conventional/classical Protein Kinase C) isoforms, which are calcium-, phospholipid-, and diacylglycerol-dependent are inhibitory where as the nPKC (novel Protein Kinase C) isoforms which are calcium independent are stimulatory for keratinocyte differentiation markers. On the right hand side is an earlier step showing the upregulation loop of TRAF2. This step occurs prior to the activation os ASK1 and the p38 cascade.

• 【试贴】过来试贴，呵呵

stemcells

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2008-03-23 21:22

Hop Pathway in Cardiac Development：
Homeodomain transcription factors comprise a large family of DNA binding factors that regulate transcription and development. Many homeodomain genes arranged in genomic clusters determine anterior-posterior patterning, while others determine the fate of cells in specific tissues. The proliferation of cardiac myocytes and their differentiation early in development are both dependent on the coordinate expression and action of serum response factor (SRF), GATA4 (see GATA pathway) and the homeodomain factor Nkx2-5. All three of these factors are expressed in developing cardiomyocytes and induce expression of cardiac genes. Disruption of the Nkx2-5 gene in mice leads to embryonic lethality and defective cardiac development. SRF also plays a duel role in cardiac development, influencing both cardiomyocyte proliferation and differentiation depending on the stage and other signals that are present.

In addition, the Hop (Homeodomain Only Protein) gene encodes a factor expressed early in cardiac development that is involved in cardiac differentiation. Hop inactivation in vertebrates leads to severe defects in cardiac development, acting downstream of Nkx2-5. Cardiac cells from mice lacking the Hop gene fail to exit the cell cycle in the normal manner, continuing to proliferate past the normal developmental stage. Many of the genes disregulated in the absence of Hop are involved in the cell cycle and are also targets of SRF. Although Hop is a homeodomain protein, it lacks a DNA-binding domain indicating that it must not regulate gene expression directly. Hop appears to regulate the expression of cardiac genes by binding to SRF and blocking DNA binding of SRF. The sequestration of SRF by Hop blocks the activation of cardiac genes, preventing normal cardiac development. The influence of Hop on the opposing processes of cardiomyocyte differentation and proliferation reflect the interaction of Hop with SRF and the duel role SRF plays. In early cardiac development, Hop opposes differentiation induction by SRF, while at later stages Hop opposes the proliferation induced by SRF.

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• 【公告】严肃考风考纪维护公平公正

stemcells

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2008-03-23 21:26

MAPKinase Signaling Pathway：
The ever evolving mitogen-activated protein kinase (MAP kinase) pathways consist of four major groupings and numerous related proteins which constitute interrelated signal transduction cascades activated by stimuli such as growth factors, stress, cytokines and inflammation. The four major groupings are the Erk (red), JNK or SAPK (blue), p38 (green) and the Big MAPK or ERK5 (light blue) cascades. Signals from cell surface receptors such as GPCRs and growth factor receptors are transduced, directly or via small G proteins such as ras and rac, to multiple tiers of protein kinases that amplify these signals and/or regulate each other.

The diagram is organized to illustrate the cascades by the background colors and also the tiers of kinases as indicated down the left hand side and separated by the horizontal dashed lines. In some cascades the first activation tier involves the MAPKKKKs, MAP kinase kinase kinase kinases or MAP4K proteins. The next tier are the serine/threonine MAPKKKs, MAP kinase kinase kinase or MAP3Ks such as RAF, TAK, ASK, and MEKK1. This level has the greatest amount of cross-communication curently known. The serine/threonine/tyrosine MAPKKs, MAP Kinase kinases or MAP2Ks, such as the MKK and MEK kinases, are one step up from the MAP kinase cascade, phosphorylating and activating these kinases. The focal tier, the MAPKs or MAP kinases includes JNK1, p38, and ERKs, and are the kinases that give each cascade its name。
BR>The endpoints of these cascades, shown in the bottom tier, includes the MAPK activated protein kinases (MAPKAPK) and some of the numerous transcription factors that regulate genes involved in apoptosis, inflammation, cell growth and differentiation。

（缩略图，点击图片链接看原图）

欢迎来干细胞与再生医学版交流讨论！ http://www.zhihuiyixue.com/bbs/post/page?bid=104&sty=1&age=30

• 【讨论】病例：双肾盂，双输尿管畸形

番茄老人

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2008-03-25 22:44

干细胞多能性的维持：
Autoinductive FGF4/Erk signaling poises embryonic stem (ES) cells for lineage
entry and must be resisted to allow self-renewal.
(A) Oct4 and Sox2 direct expression of fgf4 and poise ES cells for lineage
commitment. Elevated Erk activity provides a signal that renders pluripotent
cells susceptible to lineage inductive cues.
( Black Eye

Self-renewal of the pluripotent ES cell state requires overcoming the FGF4/
Erk signal. The actions of FGF can be (1) blocked by selective pharmacological
inhibitors of the FGF receptor (FGFR) and of Mek; (2) reversed by constitutive
expression of Nanog; (3) counteracted by blockade of commitment effectors by
the cytokine leukemia inhibitory factor (LIF) and the morphogen BMP4.

天行键，君子以自强不息地势坤，君子以厚德载物

• 【分享】抗癫痫药

番茄老人

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2008-03-25 22:49

ES细胞的分化：

This model depicts the regulation of primitive streak formation, primary germ layer induction, and tissue specification from differentiated
mouse ESCs. The first step in the differentiation pathway is the development of a population resembling the epiblast of the mouse embryo. When induced with Wnt, activin, BMP4, or serum, these cells will generate a primitive streak (PS)-like population (indicated by the row of cells outlined in blue). If these pathways are not activated, the epiblast population will differentiate into the ectoderm lineage. Ectoderm differentiation is blocked by BMP, Wnt, and activin signaling. Following PS induction, the posterior PS cells (yellow) are specified to Flk-1+ mesoderm, whereas the anterior streak cells (dark orange) are fated to generate Foxa2+ definitive endoderm. These fates are not firmly established at this stage, as activin can induce endoderm from the posterior PS population (indicated by the brown stippled arrow below the PS). The pathways that specify Flk-1 mesoderm to the hematopoietic lineage and Foxa2+ definitive endoderm to either the hepatocyte or pancreatic lineages are shown.