p****u
发帖数: 239 | 1 Shinya Yamanaka
The J. David Gladstone Institutes - USA
and
Kyoto University - Japan
Rudolf Jaenisch
M.I.T.
and
Whitehead Institute
U.S.A.
For the generation of induced pluripotent stem cells (iPS cells) from skin
cells (SY) and demonstration that iPS cells can be used to cure genetic
disease in a mammal, thus establishing their therapeutic potential (RJ). |
M*****n
发帖数: 16729 | 2 what is the hot spot in the field of iPS?
looks like to me that they have done pretty much all the fundamental
studies for this field in the animal models.
skin
【在 p****u 的大作中提到】
: Shinya Yamanaka
: The J. David Gladstone Institutes - USA
: and
: Kyoto University - Japan
: Rudolf Jaenisch
: M.I.T.
: and
: Whitehead Institute
: U.S.A.
: For the generation of induced pluripotent stem cells (iPS cells) from skin
|
A******y
发帖数: 2041 | 3 In vitro disease model; disease in a dish? For example, generate diseased neurons from skin
biopsy for the discovery of potential therapies. |
M*****n
发帖数: 16729 | 4 some people are crying for in vitro models of kidney diseases. but how can a
single type of cultured cell represent a functional renal unit in dish?
I simply don't like the idea of in vitro disease model.
for the example of neuronal diseases, I imagine it is usually late-onset and
the disease phenotype is pertinent to the neurons in the funcational domain
/circuit of the nervous system. The idea to establish such a kind of in
vitro disease model by "skin cell to iPS to neuron" is such a detour!
neurons from skin
【在 A******y 的大作中提到】
: In vitro disease model; disease in a dish? For example, generate diseased neurons from skin
: biopsy for the discovery of potential therapies.
|
p*****m
发帖数: 7030 | 5 未必
你可以做两件事，首先可以在dish里诱导分化neuron，至少现在发表的情况看，这些ne
uron是会表现出phenotype的（就是死掉了 两个例子 ALS和rett syndrome的IPS） 不
一定真
的需要多么复杂的体内环境才能表现出来。而且你也可以试图stress这些cultured neu
ron,然后只要他们死的和WT neuron不一样这个差别也可以用来screen gene/drug了
其次你还可以直接把这些iPS打到动物体内去让他们在正确的位置分化成neuron,这样可
以更好的mimic疾病环境。换句话说就是构建一个携带人源疾病组织的动物模型 这个现
在用iPS的lab很多在试。
这两个无论哪一个都比之前的animal model好得多得多。
a
and
domain
【在 M*****n 的大作中提到】
: some people are crying for in vitro models of kidney diseases. but how can a
: single type of cultured cell represent a functional renal unit in dish?
: I simply don't like the idea of in vitro disease model.
: for the example of neuronal diseases, I imagine it is usually late-onset and
: the disease phenotype is pertinent to the neurons in the funcational domain
: /circuit of the nervous system. The idea to establish such a kind of in
: vitro disease model by "skin cell to iPS to neuron" is such a detour!
:
: neurons from skin
|
M*****n
发帖数: 16729 | 6 inducing human iPS in mice or other animals? that will be cool, and I will
be surprised to see that human iPS can receive sufficient instructions in
mice to become the right cell type: this bridges/breaks the boundary between
species!
the first example is certainly useful for modeling idiopathic diseases in
dish, but further scrutinization is warranted to determine how
representative the invitro model is. for example is the ALS neurons in vitro
the same type of neuron in vivo that is afflicted by the disease? |
s******s
发帖数: 13035 | 7 //nod. 没人保证能solve所有的问题，能多解决一部分就很好了。
再说，现在也有一些在人工结构上分化啥的。
不过，iPS的identity很可疑啊，分化出来的细胞也很可疑
ne
neu
【在 p*****m 的大作中提到】
: 未必
: 你可以做两件事，首先可以在dish里诱导分化neuron，至少现在发表的情况看，这些ne
: uron是会表现出phenotype的（就是死掉了 两个例子 ALS和rett syndrome的IPS） 不
: 一定真
: 的需要多么复杂的体内环境才能表现出来。而且你也可以试图stress这些cultured neu
: ron,然后只要他们死的和WT neuron不一样这个差别也可以用来screen gene/drug了
: 其次你还可以直接把这些iPS打到动物体内去让他们在正确的位置分化成neuron,这样可
: 以更好的mimic疾病环境。换句话说就是构建一个携带人源疾病组织的动物模型 这个现
: 在用iPS的lab很多在试。
: 这两个无论哪一个都比之前的animal model好得多得多。
|
d******r
发帖数: 124 | 8 Rett syndrome那个paper我觉得挺玄乎，在culture里的Neuronal phenotype和实际的
pathogenesis差得挺远的。我觉得更好的一个例子是Lorenz Studer的familial
dysautonomia的paper，细胞水平的phenotype和疾病病理直接相关，这样就可以用iPS做
HTS了。
http://www.nature.com/nature/journal/v461/n7262/full/nature0832
ne
neu
【在 p*****m 的大作中提到】
: 未必
: 你可以做两件事，首先可以在dish里诱导分化neuron，至少现在发表的情况看，这些ne
: uron是会表现出phenotype的（就是死掉了 两个例子 ALS和rett syndrome的IPS） 不
: 一定真
: 的需要多么复杂的体内环境才能表现出来。而且你也可以试图stress这些cultured neu
: ron,然后只要他们死的和WT neuron不一样这个差别也可以用来screen gene/drug了
: 其次你还可以直接把这些iPS打到动物体内去让他们在正确的位置分化成neuron,这样可
: 以更好的mimic疾病环境。换句话说就是构建一个携带人源疾病组织的动物模型 这个现
: 在用iPS的lab很多在试。
: 这两个无论哪一个都比之前的animal model好得多得多。
|
|
M*****n
发帖数: 16729 | 9 I don't see the strength of iPS in modeling monogenic diseases. why not
simply knock-out or knock-in?
for multigenic or idiopathic diseases, iPS certainly has its edge.
iPS做
【在 d******r 的大作中提到】
: Rett syndrome那个paper我觉得挺玄乎，在culture里的Neuronal phenotype和实际的
: pathogenesis差得挺远的。我觉得更好的一个例子是Lorenz Studer的familial
: dysautonomia的paper，细胞水平的phenotype和疾病病理直接相关，这样就可以用iPS做
: HTS了。
: http://www.nature.com/nature/journal/v461/n7262/full/nature0832
:
: ne
: neu
|
m*p
发帖数: 226 | 10 It is more than modeling, iPS might cure the diseases, if it is monogenic
diseases. You can genetically modify
the iPS and then transplant the cells back to the patients.
【在 M*****n 的大作中提到】
: I don't see the strength of iPS in modeling monogenic diseases. why not
: simply knock-out or knock-in?
: for multigenic or idiopathic diseases, iPS certainly has its edge.
:
: iPS做
|
|
|
w**********9
发帖数: 242 | 11 I think it may all that feasible when we deal with genetical diseases
a
and
domain
【在 M*****n 的大作中提到】
: some people are crying for in vitro models of kidney diseases. but how can a
: single type of cultured cell represent a functional renal unit in dish?
: I simply don't like the idea of in vitro disease model.
: for the example of neuronal diseases, I imagine it is usually late-onset and
: the disease phenotype is pertinent to the neurons in the funcational domain
: /circuit of the nervous system. The idea to establish such a kind of in
: vitro disease model by "skin cell to iPS to neuron" is such a detour!
:
: neurons from skin
|
A******y
发帖数: 2041 | 12 Why? You can generate a entire mouse from it. It is stem cell.
【在 s******s 的大作中提到】
: //nod. 没人保证能solve所有的问题，能多解决一部分就很好了。
: 再说，现在也有一些在人工结构上分化啥的。
: 不过，iPS的identity很可疑啊，分化出来的细胞也很可疑
:
: ne
: neu
|
w**********9
发帖数: 242 | 13 it is not that easy. A doctor in Beijing called Huang, who injected
embryonic stem cells into the ruptured spinal cord in attempt to resume
axonal transmission. He meets a very skeptical success. people now begin to
work on in-organ stem cells to regenerate the damage.
【在 m*p 的大作中提到】
: It is more than modeling, iPS might cure the diseases, if it is monogenic
: diseases. You can genetically modify
: the iPS and then transplant the cells back to the patients.
|
p*****m
发帖数: 7030 | 14 受教了 能说说悬乎在那里呢？我不是做那个的 就觉得思路很对就是了。按说你在cult
ured cell里也不太可能看得到完全一样的pathology吧，我是想只要有phenotype，哪怕
是很artificial的，但是鉴于cell本身是patient来的，那么针对这个phenotype进行的
genetic/drug screen还是有可能得到endogenous的信息。
iPS做
【在 d******r 的大作中提到】
: Rett syndrome那个paper我觉得挺玄乎，在culture里的Neuronal phenotype和实际的
: pathogenesis差得挺远的。我觉得更好的一个例子是Lorenz Studer的familial
: dysautonomia的paper，细胞水平的phenotype和疾病病理直接相关，这样就可以用iPS做
: HTS了。
: http://www.nature.com/nature/journal/v461/n7262/full/nature0832
:
: ne
: neu
|
p*****m
发帖数: 7030 | 15 问题就是大部分的disease都不是monogenic啊。别的病我不太熟悉 Neurodegeneration
里面，做得最多的比如AD/PD/ALS，里面familial的可能10%都没有
【在 M*****n 的大作中提到】
: I don't see the strength of iPS in modeling monogenic diseases. why not
: simply knock-out or knock-in?
: for multigenic or idiopathic diseases, iPS certainly has its edge.
:
: iPS做
|
i*e
发帖数: 352 | 16 agree.
Neurodegeneration
【在 p*****m 的大作中提到】
: 问题就是大部分的disease都不是monogenic啊。别的病我不太熟悉 Neurodegeneration
: 里面，做得最多的比如AD/PD/ALS，里面familial的可能10%都没有
|
b****r
发帖数: 17995 | 17 不一定要完全和in vivo 一样啊
只要能让大家有一个比现有的model不一样，而且有一定理论上的优势，就是个值得一
试的东西
现在大家主要是想用这个in vitro的东西screen for drug和其他therapy了，比老鼠便
宜，周期
可能更短，有可能更接近病人的实际情况。毕竟人的干细胞是很难knockout knockin的
，而病人
的白细胞和皮肤细胞还是很容易拿到的
a
and
domain
【在 M*****n 的大作中提到】
: some people are crying for in vitro models of kidney diseases. but how can a
: single type of cultured cell represent a functional renal unit in dish?
: I simply don't like the idea of in vitro disease model.
: for the example of neuronal diseases, I imagine it is usually late-onset and
: the disease phenotype is pertinent to the neurons in the funcational domain
: /circuit of the nervous system. The idea to establish such a kind of in
: vitro disease model by "skin cell to iPS to neuron" is such a detour!
:
: neurons from skin
|
m*p
发帖数: 226 | 18 Sure, it is not that easy. It is far away. If iPS can be controlled to
differentiate to organ stem cell or like adult
stem cell in a precise way, then it is not that far.
to
【在 w**********9 的大作中提到】
: it is not that easy. A doctor in Beijing called Huang, who injected
: embryonic stem cells into the ruptured spinal cord in attempt to resume
: axonal transmission. He meets a very skeptical success. people now begin to
: work on in-organ stem cells to regenerate the damage.
|
s******s
发帖数: 13035 | 19 well，是stem，不代表正常。早期认为iPS和ESC基本就差不多，
现在发现差别还是很大的。毕竟不是生理条件下产生的。
【在 A******y 的大作中提到】
: Why? You can generate a entire mouse from it. It is stem cell.
|
A******y
发帖数: 2041 | 20 I am not a real biologist. So I might be missing something. If you
continue culture the iPS, it will be as good as ESC due to lost of
imprinting through propagation, that's why a mouse can be made from it.
【在 s******s 的大作中提到】
: well，是stem，不代表正常。早期认为iPS和ESC基本就差不多，
: 现在发现差别还是很大的。毕竟不是生理条件下产生的。
|
|
|
k***u
发帖数: 176 | 21 second on this.
应用人的细胞是很重要的一面. 一方面这个model 可以有疾病的表行,另一方面是不是
有效的screen tool再说.
【在 b****r 的大作中提到】
: 不一定要完全和in vivo 一样啊
: 只要能让大家有一个比现有的model不一样，而且有一定理论上的优势，就是个值得一
: 试的东西
: 现在大家主要是想用这个in vitro的东西screen for drug和其他therapy了，比老鼠便
: 宜，周期
: 可能更短，有可能更接近病人的实际情况。毕竟人的干细胞是很难knockout knockin的
: ，而病人
: 的白细胞和皮肤细胞还是很容易拿到的
:
: a
|
k***u
发帖数: 176 | 22 So far, long culture tend to make it worse due to suboptimal conditions.
Made a mouse doesn't mean made a normal mouse.
【在 A******y 的大作中提到】
: I am not a real biologist. So I might be missing something. If you
: continue culture the iPS, it will be as good as ESC due to lost of
: imprinting through propagation, that's why a mouse can be made from it.
|
i***R
发帖数: 663 | 23 现在iPS disease model 比较成型的还是心脏模型。
已经有好几篇patient derived LQT syndrome iPS 的文章了。这块还比较靠谱，不过用途
也有限。
比起心脏，肾脏就比较复杂了。
can a
and
domain
【在 M*****n 的大作中提到】
: some people are crying for in vitro models of kidney diseases. but how can a
: single type of cultured cell represent a functional renal unit in dish?
: I simply don't like the idea of in vitro disease model.
: for the example of neuronal diseases, I imagine it is usually late-onset and
: the disease phenotype is pertinent to the neurons in the funcational domain
: /circuit of the nervous system. The idea to establish such a kind of in
: vitro disease model by "skin cell to iPS to neuron" is such a detour!
:
: neurons from skin
|
k***u
发帖数: 176 | 24 老实说我觉得这些model 多少有点倾向性灌水的问题.不过多少是可以用人源的实验.
我觉得很难说作为一个model跟以前的比起来如何. 我觉得做为一个细胞based的 model
, 很难解释一个器官的生理病理过程.
现在好像几个center hES derived cardiomyocyte和iPS cardiomyocyte 是卖的好的,
希望有新的东西出来.
【在 i***R 的大作中提到】
: 现在iPS disease model 比较成型的还是心脏模型。
: 已经有好几篇patient derived LQT syndrome iPS 的文章了。这块还比较靠谱，不过用途
: 也有限。
: 比起心脏，肾脏就比较复杂了。
:
: can a
: and
: domain
|
