Nuclei isolation for flow analysis

From: Andrea Dewar (andrea.dewar@imvs.sa.gov.au)
Date: Mon Nov 26 2001 - 00:00:40 EST


Hi there, I've got another problem for you all...

I'm trying to isolate nuclei from CFSE stained cells so
that I can then fix and permeabilize the nuclei,
perform intranuclear staining, and analyse using flow
cytometry.

I am having great trouble with finding a suitable lysis
protocol; after the initial incubation and
centrifugation step, I am unable to recover
many "usable" nuclei. Most of the nuclei form a large
aggregate which can't be broken up by vortexing or
using a pipette.

To lyse my cells, I've been using HBSS/0.1%BSA/0.1%NP-
40 for 5 mins, or 1%NP-40 in 20mM EDTA, 50mM Tris-HCl
pH7.5 for 10 seconds.  I have included NP-40 in the
wash buffers, in concentrations ranging from 0.02% to
0.1%, and I have varied the centrifugation speed from
1600rpm to 8000rpm.

The actual lysis step is fine, and I assume the problem
is due to the DNA being sticky. Obviously these clumps
are bad for running on the flow and I've thought about
including RNAse in the lysis and wash solutions but
haven't got around to trying this yet.

Has anyone else tried to analyse isolated nuclei using
flow cytometry, or does anyone know a way around this
problem?

Thanks,

Andrea

Andrea Dewar
PhD Student
Leukaemia Research Laboratory
Institute of Medical and Veterinary Science
Adelaide
South Australia
AUSTRALIA 5000



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