RNA Detection

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3.6.1 Reverse
Transcription and PCR
Amplification



  1. Preheat thermocycler to 72C.

  2. Prepare master mix 1 and 2 and place the metal tube rack on
    ice.

  3. Retrieve LCM-isolated cell samples from 80 C.

  4. Spin down the samples in a microcentrifuge and transfer into
    PCR tube strips (optional,seeNote 16).

  5. Add 2.1μL of master mix 1 (do not pipette up and down to
    avoid loss of material) and spin down.

  6. Incubate for 3 min at 72C to open the secondary structures of
    the RNA molecules.

  7. Spin down and place back on ice (oligo dTs anneal during snap
    cooling).

  8. Add 5.45μL of master mix 2 and spin down.

  9. Initiate the RT reaction by heating samples at 42C for 90 min.
    Subsequently incubate samples at 50C for 2 min and at 42C
    for 2 min, and repeat this for 10 cycles. Finally, incubate
    samples at 70C for 15 min. The RT reaction takes approxi-
    mately 2.5 h after which samples are spun down.

  10. Prepare the PCR master mix 3, add 15μL per sample and spin
    down.

  11. Use the following program for PCR; 3 min at 98C, then
    18 cycles of (20 s at 98C, 15 s at 67C, and 6 min at 72C)
    (seeNote 17). End the PCR with a 5 min incubation at 72C.
    The PCR is approximately 2.5 h in length. Spin down the
    samples.


3.6.2 Bead Purification 1. Take the 19.5% PEG bead solution out of the fridge at least
20 min before starting the purification.



  1. Transfer cDNA (25μL) into a 96-well plate.

  2. Mix the 19.5% PEG bead solution well by vortexing.

  3. Add 25μL of the 19.5% PEG bead mix to the cDNA, set the
    pipet to 50μL and mix well by pipetting up and down ten
    times, while being careful not to produce bubbles.

  4. Cover the plate and incubate at room temperature for 8 min.

  5. Place the plate (covered) on a magnetic stand and leave for
    5 min.

  6. Take off the supernatant while being careful not to disturb the
    beads.

  7. Wash by adding 200μL of 80% ethanol toward the opposite
    side of the beads, shake gently, then remove ethanol, repeat
    once.


Spatial Transcriptomic Profiling Using LCM-seq 105
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