Cell Fate, Pluripotent Stem Cells & Probability - The Guo Lab at Yale School of Medicine

Transcript

• 00:05If we think of our
• 00:07body or our tissue organs
• 00:08are built by different
• 00:11type of cells working as
• 00:13a collection,
• 00:14It's almost like a little
• 00:15kid putting together
• 00:17blocks. The pieces together can
• 00:19be anything you want.
• 00:21So then the each different
• 00:23cell type or cell fate
• 00:25is a particular
• 00:26shaped or sized piece. They
• 00:29are
• 00:30expressing themselves,
• 00:32could either as a neuron,
• 00:33a skin, a blood.
• 00:35But imagine that the kid
• 00:38could have a masterpiece.
• 00:40The magic about this piece
• 00:42is that it can assume
• 00:43or adopt any shape. That's
• 00:46a stem cell.
• 00:52What we're trying to understand
• 00:54is how to mold
• 00:57that stem cell or any
• 00:58given cell into any particular
• 01:01piece or any particular cell
• 01:02type with absolute certainty and
• 01:04control.
• 01:06Now, you know,
• 01:08it's really not going too
• 01:10far fetched to saying if
• 01:11I take a drop of
• 01:12of your blood, that we
• 01:13can do something to the
• 01:14cells and then bring it
• 01:16all the way back to
• 01:17embryonic
• 01:18like state, and then we
• 01:20can redifferentiate
• 01:21these
• 01:22embryonic like cells to become
• 01:24neurons, to become heart, to
• 01:25become skin.
• 01:26This is what this,
• 01:28stem cell research is about.
• 01:31As great as the reprogramming
• 01:33process is,
• 01:35it is
• 01:36a coin toss. But it's
• 01:38like you have
• 01:39a coin that has one
• 01:40thousand faces,
• 01:42and we know one of
• 01:43the faces
• 01:44is going to be like
• 01:46a embryonic like state.
• 01:48But you can never know
• 01:50which one of these one
• 01:51thousand coins are going to
• 01:53be showing up as the
• 01:55face that you want. So
• 01:56this is what we're trying
• 01:58to understand.
• 01:59We want to be able
• 02:00to have the ability
• 02:02that every time we toss
• 02:04a coin, we get to
• 02:05exactly that one
• 02:12We started working with a
• 02:14particular cell type that their
• 02:16normal job are to make
• 02:18differentiated blood cells.
• 02:20These cells,
• 02:21they are fascinating
• 02:23in the sense
• 02:24if you toss these as
• 02:26the coin toss, they have
• 02:28a much, much higher chance
• 02:30landing
• 02:31on the face that we
• 02:32want them. We can videotape
• 02:34them and watch them as
• 02:36they change step by step.
• 02:39We could see that these
• 02:40cells
• 02:41that easier to change into
• 02:43a new new identity, they
• 02:45divide much more rapidly.
• 02:47So we started off really
• 02:49wondering whether this rapid division
• 02:56pluripotent stem cells
• 02:58with the resolution
• 02:59both temporarily, how frequently we
• 03:01need to
• 03:02track them or what kind
• 03:04of label we put on
• 03:05them, under what conditions. So
• 03:07it's
• 03:08iteratively,
• 03:09we learn more and more,
• 03:11to watch them really.
• 03:16The kind of principles we
• 03:18extract immediately
• 03:19seems to be informing only
• 03:21how do these blood progenitors
• 03:23that can become iPSCs.
• 03:25But I think this is
• 03:26the tool system that are
• 03:28telling us.
• 03:29If we now want to,
• 03:31say, take a drop of
• 03:33blood to reprogram into neurons
• 03:35or into cardiomyocytes,
• 03:38the same set of rules
• 03:39or knowledge or the laws,
• 03:41most likely they'll,
• 03:43apply.
• 03:45It is helping us to
• 03:47understand the larger picture.