Re: FACScalibur instrument settings for PI ploidy/apoptosis acquisition

From: Eric Van Buren (aa9080@wayne.edu)
Date: Fri Aug 03 2001 - 22:22:16 EST


Nate Regimbal and other curious parties,

Milena Cankovic did some apoptosis studies here in 1994 using the sub-G1
technique. First of all, murine lymphocytes from spleen and lymph nodes
were being studied, which were >97% in the G0/G1 phase. This is I think a
key issue when trying to use this protocol, since if you are working with
cultured cells, for example, you have a broad spectrum of cycling cells.
An apoptotic G2 cell could have the same DNA content as a viable G1 or S
cell, making it impossible to measure by this protocol alone. As far as
determining apoptotic cells from apoptotic bodies, we decided to only count
events with DNA index greater than 0.5. (Confirmation was done by DNA
laddering.) The sub-G1 peaks we observed were still gaussian, separated from
the G1 peaks, and had higher CVs than the G1 peaks.

As far as the "nuts and bolts" go, I think I put G0/G1 in channel 500 on a
1024 linear scale, and triggered on DNA content above channel 50 (DNA index
0.1,
a "cutoff" I think Dr. Zbigniew Darzynkiewicz once proposed for determining
apoptotic cells).

I think there are better methods for detecting apoptosis today. Probably
the only reason anyone today considers the sub-G1 method is because it is
relatively inexpensive.

Eric


>Hi all,
>
>How can one be sure that the sub G1 events are apoptotic events, and not just
>DNA fragment clusters of varying sizes?  Wouldn't marker statistics of the
>sub-G1 'pile' also be inaccurate, as the marked events are not actually cells,
>but fragments of DNA?  Also, regarding the presence of a sub-G1 'apoptotic'
>peak: what would cause apoptotic cells to all display slightly lower, yet
>Gaussian, DNA content?   Doesn't a sub-G1 peak mean that these cells all lost
>the same, small amount of DNA?  My apologies if this has been covered in the
>past.
>
>Cheers,
>Nate Regimbal
>PPD Discovery
>Menlo Park, CA
>
>Tim Kute wrote:
>
>> In most cases, I like to have my G1 peak start  in the 1/3 rd of the x axis
>> range.  If you are looking for apoptotic cells, you might want it higher
>> around 2/3 rd of range.  If you really want to see every event, you might
>> even want to put the scale on log and have the G1 peak at the 80% area of
>> the x axis.
>>
>> Tim Kute
>>
>> Maciej Simm wrote:
>>
>> > I'm posting this on behalf of a collegue. She's doing an assay with
>> > just PI looking at the peaks before/after incubation of her cells in
>> > pro-apoptotic drugs.  If anyone looks at PI on a Calibur, could you
>> > fill me in on the instrument settings that work the best? I would
>> > appreciate any other tips.
>> >
>> > Maciej
>> >
>> > >find out voltage settings for the PI assay. in particular ask  about
>> > >a printout of an acquisition template they use. also -
>> >
>> > >fsc    lin or log? what voltage?
>> > >ssc   same as above
>> > >fsc    s.a.a.
>> > >fl2     s.a.a.
>> > >fl3     s.a.a.
>> >
>> > >what about compensation?
>> >
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Eric Van Buren, aa9080@wayne.edu
Karmanos Cancer Institute and Immunology & Microbiology
Wayne State University, Detroit, Michigan, USA



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