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

Transcript

• 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.