Welcome and Introduction to Human Organoids and Stem Cells as Experimental Models
March 30, 2023ID9766
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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&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.