Frontiers in Toxicology,
Год журнала:
2022,
Номер
4
Опубликована: Март 7, 2022
New
Approach
Methodologies
(NAMs)
promise
to
offer
a
unique
opportunity
enable
human-relevant
safety
decisions
be
made
without
the
need
for
animal
testing
in
context
of
exposure-driven
Next
Generation
Risk
Assessment
(NGRA).
Protecting
human
health
against
potential
effects
chemical
may
have
on
embryo-foetal
development
and/or
aspects
reproductive
biology
using
NGRA
is
particularly
challenging.
These
are
not
single
endpoint
or
and
risk
assessments
traditionally
relied
data
from
Developmental
Reproductive
Toxicity
(DART)
tests
animals.
There
numerous
Adverse
Outcome
Pathways
(AOPs)
that
can
lead
DART,
which
means
defining
developing
strict
strategies
every
AOP,
predict
apical
outcomes,
neither
tenable
goal
nor
necessity
ensure
NAM-based
fit-for-purpose.
Instead,
pragmatic
approach
needed
uses
available
knowledge
exposure-led
sufficiently
protective.
To
this
end,
mechanistic
biological
coverage
existing
NAMs
DART
were
assessed
gaps
addressed
identified,
allowing
an
relies
generating
relevant
overall
mechanisms
involved
reproduction
development.
Using
cellular
processes
signalling
pathways
underlying
key
stages
development,
we
developed
broad
outline
endpoints
informative
DART.
When
compared
determine
whether
they
provide
comprehensive
when
integrated
framework,
found
them
generally
cover
developmental
evaluated
studies.
The
application
assessment
framework
illustrated
case
study.
Nature,
Год журнала:
2021,
Номер
597(7875), С. 250 - 255
Опубликована: Сен. 8, 2021
Abstract
The
cellular
landscape
of
the
human
intestinal
tract
is
dynamic
throughout
life,
developing
in
utero
and
changing
response
to
functional
requirements
environmental
exposures.
Here,
comprehensively
map
cell
lineages,
we
use
single-cell
RNA
sequencing
antigen
receptor
analysis
almost
half
a
million
cells
from
up
5
anatomical
regions
11
distinct
healthy
paediatric
adult
gut.
This
reveals
existence
transcriptionally
BEST4
epithelial
tract.
Furthermore,
implicate
IgG
sensing
as
function
tuft
cells.
We
describe
neural
populations
enteric
nervous
system,
predict
cell-type-specific
expression
genes
associated
with
Hirschsprung’s
disease.
Finally,
using
systems
approach,
identify
key
players
that
drive
formation
secondary
lymphoid
tissue
early
development.
show
these
programs
are
adopted
inflammatory
bowel
disease
recruit
retain
immune
at
site
inflammation.
catalogue
will
provide
new
insights
into
development,
homeostasis
Nature Biotechnology,
Год журнала:
2023,
Номер
41(11), С. 1557 - 1566
Опубликована: Март 6, 2023
Current
single-cell
RNA-sequencing
approaches
have
limitations
that
stem
from
the
microfluidic
devices
or
fluid
handling
steps
required
for
sample
processing.
We
develop
a
method
does
not
require
specialized
devices,
expertise
hardware.
Our
approach
is
based
on
particle-templated
emulsification,
which
allows
encapsulation
and
barcoding
of
cDNA
in
uniform
droplet
emulsions
with
only
vortexer.
Particle-templated
instant
partition
sequencing
(PIP-seq)
accommodates
wide
range
emulsification
formats,
including
microwell
plates
large-volume
conical
tubes,
enabling
thousands
samples
millions
cells
to
be
processed
minutes.
demonstrate
PIP-seq
produces
high-purity
transcriptomes
mouse-human
mixing
studies,
compatible
multiomics
measurements
can
accurately
characterize
cell
types
human
breast
tissue
compared
commercial
platform.
Single-cell
transcriptional
profiling
mixed
phenotype
acute
leukemia
using
reveals
emergence
heterogeneity
within
chemotherapy-resistant
subsets
were
hidden
by
standard
immunophenotyping.
simple,
flexible
scalable
next-generation
workflow
extends
new
applications.
Nature Reviews Genetics,
Год журнала:
2023,
Номер
24(10), С. 687 - 711
Опубликована: Фев. 3, 2023
Our
ancestors
acquired
morphological,
cognitive
and
metabolic
modifications
that
enabled
humans
to
colonize
diverse
habitats,
develop
extraordinary
technologies
reshape
the
biosphere.
Understanding
genetic,
developmental
molecular
bases
for
these
changes
will
provide
insights
into
how
we
became
human.
Connecting
human-specific
genetic
species
differences
has
been
challenging
owing
an
abundance
of
low-effect
size
changes,
limited
descriptions
phenotypic
across
development
at
level
cell
types
lack
experimental
models.
Emerging
approaches
single-cell
sequencing,
manipulation
stem
culture
now
support
descriptive
functional
studies
in
defined
with
a
human
or
ape
background.
In
this
Review,
describe
sequencing
genomes
from
modern
archaic
hominins,
great
apes
other
primates
is
revealing
new
cellular
-
including
atlases
organoids
are
enabling
exploration
candidate
causal
factors
underlie
traits.
Stem Cell Reports,
Год журнала:
2023,
Номер
18(6), С. 1255 - 1270
Опубликована: Июнь 1, 2023
In
the
past
decade,
term
organoid
has
moved
from
obscurity
to
common
use
describe
a
3D
in
vitro
cellular
model
of
tissue
that
recapitulates
structural
and
functional
elements
vivo
organ
it
models.
The
is
now
applied
structures
formed
as
result
two
distinct
processes:
capacity
for
adult
epithelial
stem
cells
re-create
niche
ability
direct
differentiation
pluripotent
self-organizing
multicellular
organogenesis.
While
these
fields
rely
upon
different
cell
types
recapitulate
processes,
both
share
challenges
around
robustness,
accuracy,
reproducibility.
Critically,
organoids
are
not
organs.
This
commentary
serves
discuss
challenges,
how
they
impact
genuine
utility,
shine
light
on
need
improve
standards
all
approaches.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(2), С. 1018 - 1018
Опубликована: Янв. 13, 2024
An
important
part
of
the
central
nervous
system
(CNS),
cerebellum
is
involved
in
motor
control,
learning,
reflex
adaptation,
and
cognition.
Diminished
cerebellar
function
results
cognitive
impairment
observed
patients
with
neurodegenerative
disorders
such
as
Alzheimer's
disease
(AD),
vascular
dementia
(VD),
Parkinson's
(PD),
Huntington's
(HD),
spinal
muscular
atrophy
(SMA),
amyotrophic
lateral
sclerosis
(ALS),
Friedreich's
ataxia
(FRDA),
multiple
(MS),
even
during
normal
aging
process.
In
most
disorders,
mainly
occurs
a
result
morphological
changes
over
time,
although
early
stages
some
AD,
also
serves
compensatory
function.
Biological
accompanied
by
circuits,
which
are
predominantly
control.
Despite
decades
research,
functional
contributions
underlying
molecular
mechanisms
remain
largely
unknown.
Therefore,
this
review
will
highlight
cellular
events
that
disrupted
process
development
disorders.
We
believe
deeper
insights
into
pathophysiological
be
essential
for
design
new
effective
strategies
neuroprotection
alleviation
