Stem
cells
contribute
to
organismal
homeostasis
by
balancing
division,
self-renewal
and
differentiation.
Elucidating
the
strategies
which
stem
achieve
this
balance
is
critical
for
understanding
homeostasis,
addressing
pathogenesis
associated
with
disruption
of
(e.g.,
cancer).
Planarians,
highly
regenerative
flatworms,
use
pluripotent
called
neoblasts
maintain
regrow
organs.
A
single
neoblast
can
rescue
an
entire
animal
depleted
from
regenerate
all
cell
lineages.
How
differentiation
clonal
expansion
are
governed
produce
required
types
unclear.
Here,
we
integrated
experimental
computational
approaches
develop
a
quantitative
model
revealing
basic
principles
growth
individual
neoblasts.
By
experimentally
suppressing
major
lineages,
elucidated
interplay
between
colony
lineage
decisions.
Our
findings
suggest
that
pre-select
their
progenitor
based
on
cell-intrinsic
fate
distribution.
Arresting
into
specific
lineages
disrupts
proliferative
capacity
without
inducing
compensatory
expression
other
analysis
colonies
consistent
decision
operate
memory
or
communication
This
simple
process
breaks
down
in
likely
because
activity
feedback
mechanisms.
uncover
essential
regulation
planarians,
distinct
those
observed
many
vertebrate
models.
These
mechanisms
enable
robust
production
diverse
types,
facilitate
regeneration
missing
tissues.
Cell,
Год журнала:
2024,
Номер
187(14), С. 3461 - 3495
Опубликована: Июнь 20, 2024
Developmental
biology-the
study
of
the
processes
by
which
cells,
tissues,
and
organisms
develop
change
over
time-has
entered
a
new
golden
age.
After
molecular
genetics
revolution
in
80s
90s
diversification
field
early
21st
century,
we
have
phase
when
powerful
technologies
provide
approaches
open
unexplored
avenues.
Progress
has
been
accelerated
advances
genomics,
imaging,
engineering,
computational
biology
emerging
model
systems
ranging
from
tardigrades
to
organoids.
We
summarize
how
revolutionary
led
remarkable
progress
understanding
animal
development.
describe
classic
questions
gene
regulation,
pattern
formation,
morphogenesis,
organogenesis,
stem
cell
are
being
revisited.
discuss
connections
development
with
evolution,
self-organization,
metabolism,
time,
ecology.
speculate
developmental
might
evolve
an
era
synthetic
biology,
artificial
intelligence,
human
engineering.
ABSTRACT
Tissue
regeneration
is
not
simply
a
local
repair
event
occurring
in
isolation
from
the
distant,
uninjured
parts
of
body.
Rather,
evidence
indicates
that
whole-animal
process
involving
coordinated
interactions
between
different
organ
systems.
Here,
we
review
recent
studies
reveal
how
remote
tissues
and
systems
respond
to
engage
regeneration.
We
also
discuss
need
for
toolkits
technological
advancements
uncover
dissect
communication
during
Current Opinion in Cell Biology,
Год журнала:
2024,
Номер
88, С. 102368 - 102368
Опубликована: Май 15, 2024
The
mitogen-activated
protein
kinase
(MAPK)/extracellular
signal-regulated
(ERK)
signaling
network
is
a
key
transducer
of
signals
from
various
receptors,
including
receptor
tyrosine
kinases
(RTKs).
It
controls
cell-cycle
entry,
survival,
motility,
differentiation,
as
well
other
fates.
After
four
decades
studying
this
pathway
with
biochemical
methods,
the
use
fluorescent
biosensors
has
revealed
dynamic
behaviors
such
ERK
pulsing,
oscillations,
and
amplitude-modulated
activity.
Different
RTKs
equip
MAPK
specific
feedback
mechanisms
to
encode
these
different
dynamics,
which
are
then
subsequently
decoded
into
cytoskeletal
events
transcriptional
programs,
actuating
cellular
Recently,
collective
wave
have
been
observed
in
multiple
systems
coordinate
dynamics
fate
decisions
within
cell
collectives.
This
emphasizes
that
correct
understanding
requires
it
at
scales.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 15, 2025
Abstract
Severe
myocardial
injuries
in
mammals
lead
to
cardiomyocyte
loss
and
heart
failure.
Activation
of
Glucocorticoid
Receptor
(GR)
by
endogenous
glucocorticoids
limit
proliferation
cardiac
regeneration.
Here,
we
reveal
that
suppress
the
proliferative
response
cardiomyocytes
a
diverse
range
regenerative
factors,
including
Neuregulin
1
(NRG1),
FGF1,
IGF2,
IGF1,
BMP7,
Oncostatin
M
(OSM),
LIF,
RANKL,
IL6,
IL13,
IL4,
IL1-beta.
Transcriptomic
analyses
revealed
glucocorticoids-GR
axis
induces
expression
MAPK/ERK
pathway
inhibitors
ERRFI1/MIG6
DUSP1.
Using
NRG1
as
model
system
for
demonstrate
growth
factor-induced
ERK
activation,
nuclear
translocation,
transcriptional
output.
Knockdown
experiments
confirmed
ERRFI1
DUSP1
are
key
mediators
glucocorticoid-mediated
suppression
induced
factors.
The
GR
target
genes,
Dusp1
Errfi1,
increases
during
early
postnatal
development,
coinciding
with
transition
post-mitotic
cardiomyocytes.
In
juvenile
adult
stage,
factors
failed
activate
induce
effectively;
however,
inhibition
rescues
these
responses.
Consistently,
antagonization
development
preserved
activity.
Importantly,
or
deletion
reinstated
growth-factor-induced
postmitotic
Finally,
enhanced
vivo
effectiveness
factor-based
therapy
an
mouse
injury,
enhancing
function.
These
findings
previously
unrecognized
mechanism
which
systemic
hormones,
specifically
glucocorticoids,
regulate
potential
paracrine
This
study
highlights
transient
glucocorticoid
promising
strategy
enhance
therapeutic
efficacy
approaches.
Highlights
Physiological
cytokines.
Glucocorticoids
inhibit
activation
upregulating
negative
regulators
ERRFI1.
Increased
glucocorticoid-induced
impairs
mitogenic
activity
restores
MAPK
signaling
enhances
therapies
following
injury.
The
activation
of
progenitor
cells
near
wound
sites
is
a
common
feature
regeneration
across
species,
but
the
conserved
signaling
mechanisms
responsible
for
this
step
in
whole-body
are
still
incompletely
understood.
acoel
Hofstenia
miamia
undergoes
using
Piwi+
pluripotent
adult
stem
(neoblasts)
that
accumulate
at
amputation
early
process.
EGFR
pathway
has
broad
roles
controlling
proliferation,
migration,
differentiation,
and
cell
survival
metazoans.
Using
candidate
RNAi
screening
approach,
we
identify
erbB4-2
Neuregulin
nrg-1
genesas
essential
blastema
formation.
Structure
prediction
NRG-1
ERBB4-2
proteins
supports
likelihood
these
factors
interacting
directly.
After
injuries,
expression
induced
body-wall
muscle
site
by
6
hours
localizes
to
tip
outgrowing
over
next
several
days,
while
broadly
expressed,
including
neoblasts.
Under
nrg-1(RNAi)
erbB4-2(RNAi)
conditions
impair
formation,
animals
undergo
earliest
responses
injury
activate
Early
Growth
Response
transcription
factor
egr,
indicating
crucial
role
downstream
initial
activation.
possess
H3P+
mitotic
neoblasts
which
hyperproliferate
normally
after
amputation,
fail
site.
Therefore,
provides
source
Neuregulin-ErbB
necessary
mobilization
proliferative
progenitors
enable
outgrowth
Hofstenia.
These
results
indicate
shared
functional
requirement
between
planarians
acoels
550
million
years
evolution.
Stem
cells
contribute
to
organismal
homeostasis
by
balancing
division,
self-renewal
and
differentiation.
Elucidating
the
strategies
which
stem
achieve
this
balance
is
critical
for
understanding
homeostasis,
addressing
pathogenesis
associated
with
disruption
of
(e.g.,
cancer).
Planarians,
highly
regenerative
flatworms,
use
pluripotent
called
neoblasts
maintain
regrow
organs.
A
single
neoblast
can
rescue
an
entire
animal
depleted
from
regenerate
all
cell
lineages.
How
differentiation
clonal
expansion
are
governed
produce
required
types
unclear.
Here,
we
integrated
experimental
computational
approaches
develop
a
quantitative
model
revealing
basic
principles
growth
individual
neoblasts.
By
experimentally
suppressing
major
lineages,
elucidated
interplay
between
colony
lineage
decisions.
Our
findings
suggest
that
select
their
progenitor
based
on
cell-intrinsic
fate
distribution.
Arresting
into
specific
lineages
disrupts
proliferative
capacity
without
inducing
compensatory
expression
other
analysis
colonies
consistent
decision
operate
memory
or
communication
This
simple
process
breaks
down
in
likely
because
activity
feedback
mechanisms.
uncover
essential
regulation
planarians,
distinct
those
observed
many
vertebrate
models.
These
mechanisms
enable
robust
production
diverse
facilitate
regeneration
missing
tissues.
Genes,
Год журнала:
2025,
Номер
16(4), С. 365 - 365
Опубликована: Март 22, 2025
Background:
Metformin
is
a
widely
used
oral
hypoglycemic
agent
for
treating
type
2
diabetes.
Planarians,
with
their
remarkable
regenerative
abilities,
are
frequently
employed
as
model
organisms
in
stem
cell
and
regeneration
studies.
This
study
aimed
to
investigate
the
effects
of
metformin
on
planarian
regeneration,
focusing
eyespots
after
amputation.
Methods:
Regenerating
planarians
amputated
were
exposed
various
concentrations
metformin.
The
time
was
measured
assess
Subsequently,
1
mmol/L
treatment
24
h
applied
planarians,
followed
by
transcriptome
analysis
identify
differentially
expressed
genes
(DEGs).
gene
expression
validated
through
qPCR.
full-length
casein
kinase
1α
(DjCK1α)
cloned
using
RACE
technology.
DjCK1α
interference
performed
examine
its
role
regeneration.
Results:
Low
significantly
reduced
planarians.
Transcriptome
identified
113
DEGs,
including
61
upregulated
52
downregulated
genes.
GO
KEGG
enrichment
analyses
conducted.
Notably,
DjCK1α,
key
involved
selected
further
validation.
qPCR
confirmed
that
upregulated.
prolonged
cultured
water,
while
did
not
promote
eyespot
DjCK1α-interfered
Conclusions:
results
suggest
accelerates
potentially
regulation
DjCK1α.
provides
first
transcriptome-based
drug
highlighting
process.
Communications Biology,
Год журнала:
2023,
Номер
6(1)
Опубликована: Ноя. 9, 2023
Abstract
The
potential
for
basic
research
to
uncover
the
inner
workings
of
regenerative
processes
and
produce
meaningful
medical
therapies
has
inspired
scientists,
clinicians,
patients
hundreds
years.
Decades
studies
using
a
handful
highly
model
organisms
have
significantly
advanced
our
knowledge
key
cell
types
molecular
pathways
involved
in
regeneration.
However,
many
questions
remain
about
how
unfold
regeneration-competent
species,
they
are
curtailed
non-regenerative
organisms,
might
be
induced
(or
restored)
humans.
Recent
technological
advances
genomics,
biology,
computer
science,
bioengineering,
stem
hold
promise
collectively
provide
new
experimental
evidence
different
accomplish
process
In
theory,
this
should
inform
design
clinical
approaches
medicine.
A
deeper
understanding
tissues
organs
regenerate
will
also
undoubtedly
impact
adjacent
scientific
fields.
To
best
apply
adapt
these
technologies
ways
that
break
long-standing
barriers
answer
critical
regeneration,
we
must
combine
deep
developmental
evolutionary
biologists
with
hard-earned
expertise
scientists
mechanistic
technical
end,
perspective
is
based
on
conversations
from
workshop
organized
at
Banbury
Center,
during
which
diverse
cross-section
regeneration
community
experts
various
discussed
enduring
biology.
Here,
share
group
identified
as
significant
unanswered,
i.e.,
known
unknowns.
We
describe
obstacles
limiting
progress
answering
expanding
number
diversity
used
essential
deepening
capacity.
Finally,
propose
investigating
problems
collaboratively
across
network
researchers
advance
field
unexpected
insights
into
important
related
areas
biology
