Welcome and Introduction to Human Organoids and Stem Cells as Experimental Models

March 30, 2023

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00:00Welcome everyone to this Symposium
00:04Human development and organize them.
00:06Sets of experimental models,
00:08somatic mosaices,
00:10developmental disorders and beyond.
00:13Very glad that we were allowed to do this.
00:17Thanks to the Dean for allowing
00:20to organize this workshop.
00:21Thank you for coming.
00:23And my name is Flora Vacarino.
00:25I'm the hardest professor at
00:27the Child Study Center and
00:28Department of Neuroscience at Yale.
00:30And I wanted to just say a few things.
00:34There will be a survey at the end of the
00:37workshop that you are invited to respond.
00:40And we're not going to have a Q&amp;A
00:44at the end of each presentation
00:46just because of lack of time.
00:48But we do have a break.
00:52And so 15 minutes break.
00:54So you are all invited to talk
00:56to each other during that time.
00:59Also, there are restrooms, of course,
01:03outside just outside of the room.
01:05So let me start by introducing
01:07somebody who needs no introduction,
01:10our Dean, Doctor Nancy Brown.
01:13She graduated from New York
01:15College and her medical degree
01:17from Harvard University completed
01:19her internship and residency.
01:21In medicine at Vanderbilt University
01:24and then did a fellowship in
01:26clinical pharmacology there.
01:28And in in 2020,
01:29she became the Jean and David
01:32Wallace Dean of Medicine and
01:34CNH Long professor of internal
01:37medicine at Yalesboro Medicine.
01:41So thank you Dean Brown,
01:42please come to the podium.
01:50So that the pleasure is mine.
01:51I've been looking forward to this
01:54workshop for for weeks and talking
01:56today about human organoids and
01:59induce potent stem cells and I need
02:02not tell this argue this audience.
02:04This technology has been transformative
02:07in helping us to understand developmental
02:10processes to understand the effect
02:12of somatic mutations and I'm really
02:15is giving the potential we giving
02:17rise to cell based therapeutics.
02:20What you're going to hear about today are,
02:22I think, technological advances
02:24that can accelerate this work,
02:27as well as information about plasticity
02:30and increased understanding and
02:32developmental programming and again,
02:36new ways of understanding the impact
02:39of of altered gene regulation.
02:42You're going to hear in particular
02:46from Doctor Alexei Abhisov,
02:47who has joined us from Mayo.
02:50And I can only say it is so exciting
02:53to have a guest speaker here in three
02:56dimensions and not on the screen.
02:58And he will speak about somatic mutations,
03:01reveal personal history and
03:04of development and aging.
03:06I I want to thank those of you
03:08who were involved in organizing,
03:10particularly Flora.
03:11Also hyphen for your leadership and
03:15I'm going to sit down and listen.
03:17So thanks for coming.
03:24Well, thank you very much, Dean Brown.
03:27And let me now introduce Doctor Lynn Hyphen.
03:32Lynn Hyphen is the Eugene Higgins professor
03:35of cell biology and professor of genetics,
03:38obstetrics and gynecology and
03:40reproductive sciences and dermatology
03:42at Yale School of Medicine.
03:45And he's the director of the
03:47well known Yao Stem Cell Center.
03:49And him and I will give you a
03:52brief overview of the symposium,
03:58please. Thank you very much for your
04:00kind introduction and I also wanna thank
04:03Nancy for your invigorating remarks.
04:05Good afternoon, everyone.
04:07You know, as Tim Brown alluded to,
04:10the advent of human organoids
04:13really represents a major
04:15advancement in the stem cell field.
04:17These in visual cultured 3D stem
04:22cell derived systems will allow us to
04:25study human development and diseases
04:28in ways that otherwise not possible,
04:32and they also can mimic our
04:35human organ development.
04:36Truly in a remarkable detail that we can use
04:40it for many other important applications.
04:43And at Yale we actually have a
04:45vibrant community of human organized
04:48researchers who are conducting cutting
04:50edge research in this exciting subject.
04:53And thanks to Dean Brown and associate
04:56Dean Luce Montgomery's vision and
04:59strong support on this timely topic,
05:01and also thanks to Professor Flora Vecranos.
05:07Effort in spearheading its
05:08organization today,
05:09we really have some of the most
05:12achieved human organo researchers
05:14on campus to share with us.
05:17They are very exciting research
05:18and we are very fortunate to
05:21have Professor Alexei Avizov,
05:23who actually is a Yale alumnus,
05:26coming back to Yale to enlighten us on
05:29his work on the somatic genetic variance
05:32impact on human development disease.
05:35And this workshop really
05:37is a Flora's when child.
05:39And Flora has really invented the
05:41sanctions banquet of knowledge for us.
05:43So now,
05:43actually,
05:43I'd like to invite Flora to say
05:45a few words about the workshop.
05:46Thank
05:47you. You're welcome. Thank you.
05:50OK, so let's start with the specifics.
05:54What's an organoid? An organoid is
05:59a collection of pluripotent cells.
06:02Or stem cells that will develop together into
06:05a mimic of an organ, a model of an organ.
06:10So these sets grow and develop together.
06:12That's the definition of an organoid.
06:14And because it's coming originally from
06:17STEM or progenitive sets, those can
06:19actually be derived from a living person.
06:23So that's really the breakthrough that
06:26Yamaraka discovered many years ago.
06:29And now, thanks to this,
06:31what can we do with this?
06:33Well, we can understand something
06:37called human diversity.
06:38And this is a subject that I'm
06:40very passionate about. And it can.
06:42It comes from more than 20 years
06:45studying the human genome.
06:46We're all very different from each other.
06:49We're different at the.
06:51Genomic level,
06:52the part that we inherited from
06:54our parents who are also different
06:56at the level of somatic mutations,
06:58which as Alexei will tell us,
06:59accumulate over each other over life,
07:03during life.
07:05So that's an additional source of
07:07differences that is individual.
07:08And then we were different at the
07:11level of epigenomic alterations that
07:13model the DNA in 3D confirmation
07:16that are peculiar for each person
07:19and regulate gene expression.
07:21And this could be also modulated
07:22by the environment.
07:23So altogether makes each one of
07:25us unique with respect to another.
07:28And the organoids is probably the
07:30only opportunity we have to study
07:33how this development,
07:35this developmental trajectory are
07:37different across individual people.
07:40And the implication from for
07:42disorders is profound because
07:44although this model is still imperfect.
07:48Has the potential to model also
07:52susceptibility to various disorders and
07:55there therefore inform therapeutics,
07:58prevention and all and all of the above.
08:01So thank you very much for coming.