发信人: Marble (小石头哥哥), 信区: Biology
标 题: Re: MCBJC(Neurogenesis/adult neural stem cell)
发信站: The unknown SPACE (Wed Apr 9 17:20:49 2003), 站内信件

【 在 macromind (星雨) 的大作中提到: 】
: 【 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
very good points. while you have listed so many answers that
others could not participate, i have to ban you. hehe.
as for the functional analysis, i think a long-term in vivo
observation is important if the final goal is for clinics.
however, when i talked with Fred Gage, he did not seem to be
interested; one reason i think is that stem cell research is
not welcomed by the politicians and its clinical prospect is
still shaddowed. btw, there are too many unknowns, and it is
still not applicable for such bold exploration. to find the
molecules that are essential to astrocyte promoted neurogenesis,
i have also thought about analysis of the difference b/w
spinal chord and hippocampus. besides microarray (for total
RNA and polysomal RNA that is termed to being translated ),
i would like to screen for pharmcological molecules that
interrupt with this process (too risky). biochemical analysis
of the diffusible factors is quite important, as you have
mentioned. it may be interesting to fractionate such peptides
or hormones and test the effects on NSC, and determine the
dosage response. meanwhile, i would consider investigation
of genetically modified neural stem cell and astrocytes,
particularly if the expression of certain key genes could
be controlled during this process.

: 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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