发信人: macromind (星雨), 信区: Biology
标 题: Re: MCBJC(Neurogenesis/adult neural stem cell)
发信站: The unknown SPACE (Mon Apr 7 20:26:27 2003), 站内信件
【 在 Marble (小石头哥哥) 的大作中提到: 】
: this Nature paper (2002 417:39) addressed the mechanisms that
: control fate of neural stem cells. astrocytes have been
: thought merely as supportive cells in the central nervous
: system, however, this work has demonstrated that astrocytes
: isolated from adult hippocampus, but not spinal chord,
: promoted neurogenesis (i.e., neuron fate) of the adult neural
: stem cells in cell culture. this study has highlighted the
: effects of the environment on the specification of stem cells.
: for stem cell research, many labs try to identify the key
: features for cells that have "stemness", and how they could
: be induced to differentiate into different lineages, and
: whether different lineages could "transdifferentiate". it is
: rather new area with many things unknown, and even experiments
: that had doubt on previously published data could get onto
: top journals.
: my questions for this paper:
: 1. what are the methodology they used to study differentiation
: of neural stem cells? do you think there might be flaw for such
: study (for example, primarily in vitro cell culture; counting
: cells with differentiation marker really means that the cells
: have differentiated into functional states)?
To study NSC differentiation, GFP and differentiation maker can be used in
vitro, which is relatively easy. In vivo differentiation
studies usually adopt 2 strategies: transplantation or retroviral injection
to trace the progenies of NSC. People have done that,
showing that different cell types are generated, but it's really hard to say
these different progenies are from the same SINGLE
ancestor. Till now, I think there is still NO convicing evidence to demostra
te NSC existence in vivo. Some people even think only
progenitors exist over there, and astrocytes are the bona fide stem cells.
You made a very good point arguing that those markers are not necessarily id
entities of specific cell types. Actually as many labs
show, MAPab can also react with astrocytes and/or oligodendrocytes. But in t
his experiment, MAPab+ cells are certainly not
GFAP+ or RIP+, suggesting that MAPab+ are mostly, although not exclusively,
neurons.
: 2. they proposed that cell-attached and diffusible factors from
: astrocytes are essential to the neurogenesis of adult stem
: cells. how would you like to identify and characterize such
: factors biochemically and genetically?
Biochemically, we can purify the factors from the conditioned medium and to
assay their activity to regulate neurogenesis. Actually
the same lab identified CCg which is required for NSC proliferation and neur
ogenesis. Obviously there are many other factors remain
unidentified. Microarray to compare SC- and Hippacampal astrocyte may get a
lot of information. I don't know and have interests in
listening your genetical approches.
: 3. btw, Dr. Song also had a publication on Nat Neuro 2002
: 5:438 in which he demonstrated that these stem cells had
: functionally integrated into the system using electrophysiology.
: i would think that in vivo transplantation and a long-term
: project chasing the fate of the neural stem cells would be
: more convincing.
In vivo tracing of the NSC fates by either transplantation or retroviral mak
er have been done previously. But those experiments are
hard to reveal the active regulatory role of astrocytes, because of the hete
rogenous nature of cell composition in neurogenic region of
DG. The massive astrocytic background in culture might, I guess, conveys som
e information of lack of functional neurons, thus
instructs NSC (probably SOME astrocytes themselves) to become neurons.
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※ 来源:.The unknown SPACE bbs.mit.edu.[FROM: 162.129.]
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