活细胞就是干细胞？

sunsong7

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张也行 发表于 2011-5-16 22:20 7 k1 Y0 c0 g8 R
回复 sunsong7 的帖子
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"如果终末细胞不具备进行“复制”或“增殖”的潜能还不能被称为“细胞”"

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关于不能复制的细胞是否还算“细胞”？这个问题请参看前面贴子关于细胞的定义（http://www.stemcell8.cn/forum-re ... 657-pid-360678.html）$ u8 b% k  a0 x
另外，一些研究表明除了“重编程”技术外，病毒感染、细胞微环境改变等因素可以再激活终末分化细胞进入细胞周期，说明终末分化细胞仍具有可塑性。$ I$ f/ B1 i2 o7 {( a7 P

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2 r1 `& E' K& @) X% I/ {' m' F) A【扩展阅读】. i5 r$ }" k( r" [- s
通常理解，终末分化细胞(terminally differentiated cells) 又称不育细胞或不分裂细胞，指一旦生成后，终生不再分裂的高度分化的成熟细胞。简单地说就是最后定型的细胞，干细胞进入终末分化后，形成执行特定功能的成熟细胞，不再分裂，譬如运输氧气的红细胞、成熟表皮细胞、神经元、成熟的浆细胞等等。8 F( J6 V: k/ \9 @* i4 {. A
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类似的概念还有永久性细胞（permanent cells）是指不具有再生能力的细胞，此类细胞出生后即脱离细胞周期，永久停止有丝分裂。 属于此类的有神经细胞（包括中枢的神经元和外周的节细胞），另外心肌细胞和骨骼肌细胞再生能力也极弱，没有再生修复的实际意义，一旦损伤破坏则永久性缺失，代之以瘢痕性修复。& k2 R2 S* b6 C; A+ N: b, K7 v. D
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下面的资料表明这些观点正在被颠覆：
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2 A$ I* ^! [$ F& h2 T. uTerminally differentiated skeletal myotubes are not confined to G0 but can enter G1 upon growth factor stimulation （终末分化细胞并不仅锁定于G0期，细胞因子可以刺激其进入G1期）* M$ S: c+ C7 {- m# G
M Tiainen, D Pajalunga, F Ferrantelli, S Soddu, G Salvatori, A Sacchi and M Crescenzi ' o8 S) e- S, q2 S* Y2 W
Molecular Oncogenesis Laboratory Regina Elena Cancer Center, Rome, Italy.
' h# n, ~( l5 z5 C  RCell Growth & Differentiation, Vol 7, Issue 8 1039-1050, Copyright © 1996 by American Association of Cancer Research 6 c. c5 n  B/ y# `+ R: e
Terminally differentiated cells are specialized cells unable to proliferate that constitute most of the mammalian body. Despite their abundance, little information exists on the characteristics of cell cycle control in these cells and the molecular mechanisms that prevent their proliferation. They are generally believed to be irreversibly restricted to the G0 state. In this report, we define some features of a paradigmatic terminally differentiated system, the skeletal muscle, by studying its responses to various mitogenic stimuli. We show that forced expression of a number of cell cycle-regulatory genes, including erbB-2, v-ras, v-myc, B-myb, ld-1, and E2F-1, alone or in combinations, cannot induce terminally differentiated skeletal muscle cells (myotubes) to synthesize DNA. However, serum-stimulated myotubes display a typical immediate-early response, including the up-regulation of c-fos, c-jun, c-myc, and ld-1. They also elevate the expression of cyclin D1 after 4 hours of serum treatment. All these events take place in myotubes in a way that is indistinguishable from that of quiescent, undifferentiated myoblasts reactivated by serum. Moreover, pretreatment with serum shortens the time required by E1A to induce DNA synthesis, confirming that myotubes can partially traverse G1. Serum growth factors do not activate late-G1 genes in myotubes, suggesting that the block that prevents terminally differentiated cells from proliferating acts in mid-G1. Our results show that terminally differentiated cells are not confined to G0 but can partially reenter G1 in response to growth factors; they contribute to a much-needed definition of terminal differentiation. The important differences in the control of the cell cycle between terminally differentiated and senescent cells are discussed. + I# L, u0 N- w7 y, h

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! |6 R) q5 e- KReactivation of the Cell Cycle in Terminally Differentiated Cells （终末分化细胞的细胞周期再激活）
0 a1 {- _1 ^# a& `3 t6 K4 @Molecular Biology Intelligence Unit 17, by Marco Crescenzi，  Publisher: Springer 2003
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6 g' N4 m# M8 q+ @4 BTerminal differentiation is defined as the state in which a cell has acquired specialized properties and has ceased proliferating permanently. This book comprehensively describes whether the terminally differentiated state actually exists, the molecular mechanisms that control the post-mitotic state, and whether terminally differentiated cells can be induced to proliferate in a stable, controllable and reversible fashion.& w  Z) C! X$ S% Z3 W* a0 J

4 y4 C; o: L% I7 k8 SThis volume deals with the most advanced areas of reactivation of the cell cycle in terminally differentiated cells. Terminally differentiated cells have long been regarded as irreversibly unable to proliferate. However, this view is being overturned, with great implications for both biological knowledge and potential therapeutic applications.
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0 l$ [+ U) k9 ]+ O- yTable of Contents
  b/ @9 H/ F3 l' j6 y3 PReactivation of Terminally Differentiated Cells: Introduction     Marco Crescenzi4 S2 r) W; G/ x$ f) [( T: A, j# r# A# r
Cell cycle reactivation in skeletal musce cells     Marco Crescenzi
! _4 Z" A7 j+ g, p3 {9 p/ bMyocyte Proliferation in the Failing Heart      Piero Anversa/ B( C% G& J. S! T
Reversal of terminally differentiated state in skeletal myocytes by SV40 large T antigen     Takeshi Endo
6 n& F% E6 c, B& qRegulation of proliferation and apoptosis in the cardiac myocyte      Loren J. Field ) k9 B# p% W% R& n
The "Post-mitotic" Phenotype in Cardiac Muscle Cells     Michael D. Schneider
3 S1 B2 E& ]- i- y4 SCellular de-differentiation during regeneration: the amphibian muscle system     Elly M. Tanaka * `: L5 F3 ^# V
【在线阅读】http://www.ccebook.net/preview/0 ... ifferentiated-cells& C! K4 }) X3 s2 x# h" ?; e5 _1 x$ `% @
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Mitotic cycle reactivation in terminally differentiated cells by adenovirus infection. (腺病毒感染可再激活终末分化细胞进行有丝分裂)
( w" V! Y: T0 s9 C4 X, IJournal of cellular physiology, Vol. 162, No. 1. (January 1995), pp. 26-35. doi:10.1002/jcp.1041620105 Key: citeulike:3503872
; {7 S. {2 g/ l8 [, ]* QDifferent cell types (e.g., neurons, skeletal and heart myocytes, adipocytes, keratinocytes) undergo terminal differentiation, in which acquisition of specialized functions entails definitive withdrawal from the cell cycle. Such cells are distinct from quiescent (reversibly growth-arrested) cells, such as contact-inhibited fibroblasts. Terminally differentiated cells can not be induced to proliferate by means of growth factor stimulation or transduction of cellular oncogenes. An important first step toward defining the molecular basis for such unresponsiveness is to find a practical means to overcome the proliferative block. Furthermore, determining whether terminally differentiated, postmitotic cells still retain a potential competence for proliferation that can be reactivated would have important theoretical and practical implications. To address these questions, we exploited the properties of adenoviruses. These viruses can infect postmitotic cells and express E1A, a powerful activator of proliferation in reversibly growth-arrested cells. We infected terminally differentiated skeletal muscle cells and adipocytes with human adenovirus type 5 or 12, obtaining full reentry into the cell cycle, including DNA synthesis, mitosis, cytokinesis, and extended proliferation. Similar results were obtained with established cell lines and primary cells belonging to several species, from quail to humans. Genetic analysis indicated that the smaller splice product of E1A, E1A 12S, is sufficient to induce cell cycle reactivation in otherwise permanently nonmitotic cells. These results demonstrate that terminally differentiated cells retain proliferative potential and establish adenovirus as a convenient and powerful means to force such cells to reenter the cell cycle.  （http://www.citeulike.org/user/giovenko/article/3503872）
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sunsong7

张也行 发表于 2011-5-17 09:16 0 _* M5 X  l! t/ y
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( {% B% v, t2 V& d5 u  C$ ^如果你这样定义细胞和活细胞的话，那么你相当于在说：所有的细胞，除了不是干细胞的 ...

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“活细胞就是干细胞”可以这样理解，所有具有完整细胞结构和功能细胞都具有可塑性，都是干细胞研究的对象；
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另外不建议采用marker来定义干细胞，首先marker表达与细胞功能之间的关系具有不确定性，且容易受微环境影响发生改变；其次，许多marker在不同细胞谱系间存在交叉；更要命的是无论“干细胞（dry cell）”还是“湿细胞（dead cell）”都有相似的marker。

sunsong7

回复 张也行 的帖子
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很幸运“活细胞就是干细胞”这个话题能得到大家的批判，当初是marrowstem关于“干细胞演化——the Origin of Disease”的命题引起老狼思索，注意到我们头脑中一些根深蒂固的概念正在被干细胞所刷新...
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在此老狼倡导论坛成员更多地采用一些批判性思维（CriticalThinking）: r% r$ L! H1 B
             ——问题比答案重要http://www.stemcell8.cn/thread-39581-1-1.html

sunsong7

回复 weiyepan 的帖子8 P% j6 I- j- v9 d& D# \

1 }. [( x# H3 b/ j9 |2 C个人认为多能干细胞分裂（分化）的marker在分裂前后总数是不一致的：5 B% }. a& {& C# p+ _# P) a! S
1. 对称分裂： 虽然进入细胞周期的干细胞体积会长大，对称分裂后两个子细胞细胞体积仍要进一步增大，那么，两个子细胞的marker总数相对于分裂前母细胞应该略有增加；而两个子细胞的marker总数与处于相对同一细胞周期阶段的母细胞来说总体上应该加倍；
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2. 不对称分裂(分化)：这种情况更复杂一些，两个子细胞的marker总数相对于分裂前母细胞来说可能增加也可能减少。因为marker是蛋白质有一定的寿命，不对称分裂的后代某些marker不再表达，原有一些不需要的特异性marker就会逐渐脱落或被降解。

sunsong7

回复 Dzz 的帖子; P4 |! T' y; r) J) g1 e! Z

3 [& T$ z" f/ I4 ~# V非整合基因的细胞重编程技术给出了答案：活细胞在合适的条件下可以被诱导成iPS细胞，都具有分化全能性...

sunsong7

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回复 头脑和灵魂 的帖子5 e! I$ I6 }  T9 y: ], g7 U
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欢迎参加讨论，干细胞定义目的是为了确定干细胞的研究对象在细胞综合分类系统中的含义、位置、界限和规定，随着人类认知能力提升干细胞的定义在悄然改变；6 W0 I3 S3 [4 a
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本贴从目前较普遍被接受的定义出发讨论干细胞研究对象界定问题，仅试图说明“白猫、黑猫、老猫和小猫都是猫”，尚未尝试对干细胞进行重新定义。

sunsong7

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+ W* t! D2 [& }/ V回复 cochongg 的帖子
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" D: S% p7 Q: g- G: _1 @4 {楼上偷换了概念，不要把“红细胞（红血球）”说成是“活细胞”。
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! y4 n# Y5 F# V$ F/ Q' }  @3 c细胞的定义为“能进行独立繁殖的有膜包围的生物体的基本结构和功能单位。一般由质膜、细胞质和核（或拟核）构成，是生命活动的基本单位”。这个定义包含两层含义：
% O* T/ T' ~% v$ G0 p5 u    1. 结构——细胞由“质膜、细胞质和核（或拟核）”等构成；* g; ^" q3 j$ Q
    2. 功能——细胞能进行“独立繁殖”或新陈代谢。
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    红血球由膜包围32％血红蛋白、64％水分和4％的脂质、糖类和各种电解质组成，没有细胞核、线粒体、高尔基体、或核糖体等细胞器，不具有细胞的基本结构； 红血球不进行核酸复制、不进行蛋白质合成，也没有基本的信息和能量交换，仅参与携氧和带出二氧化碳的氧化还原反应，没有生命的新陈代谢能力，不会衰老或凋亡。因此，红血球不是细胞。
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+ `+ }7 F& W6 A    机体中除红血球外，还有许多有生理活性而非细胞的成分，如：血小板、酶、细胞因子、抗体、核酸、糖、脂肪等，如果把这些构件重新组装起来制造“活细胞”应该属于“合成生物学”研究的范畴。- U, n* J- I7 p- ~

( s4 C: b  h3 N  J) h' Q4 s7 t    另外，研究表明传统意义上许多不具有再生能力的神经细胞、肌肉细胞、骨骼细胞、脂肪细胞等“终末分化细胞”均可被再激活而进入细胞周期，参见： http://www.stemcell8.cn/forum-re ... 657-pid-361782.html. X( n' [8 g  t1 r

. I1 f/ [' p( y! B0 T1 |    本贴的主旨不是为了重新定义“干细胞”，而是讨论如何界定干细胞研究对象。- Z4 q; l) Y9 z5 k2 w( `