Nature,
Journal Year:
2021,
Volume and Issue:
597(7876), P. 387 - 392
Published: Aug. 25, 2021
Starting
from
the
zygote,
all
cells
in
human
body
continuously
acquire
mutations.
Mutations
shared
between
different
imply
a
common
progenitor
and
are
thus
naturally
occurring
markers
for
lineage
tracing1,2.
Here
we
reconstruct
extensive
phylogenies
of
normal
tissues
three
adult
individuals
using
whole-genome
sequencing
511
laser
capture
microdissections.
Reconstructed
embryonic
progenitors
same
generation
phylogeny
often
contribute
to
extents
body.
The
degree
this
asymmetry
varies
individuals,
with
ratios
two
reconstructed
daughter
zygote
ranging
60:40
93:7.
Asymmetries
pervade
subsequent
generations
can
differ
individual.
resolve
spatial
patterning
tissues,
revealing
contiguous
patches
of,
on
average,
301
crypts
colonic
epithelium
derived
most
recent
cell
also
effect
brain
development.
Using
data
ten
additional
men,
investigated
developmental
split
soma
germline,
results
suggesting
an
extraembryonic
contribution
primordial
germ
cells.
This
research
demonstrates
that,
despite
reaching
ultimate
tissue
patterns,
early
bottlenecks
commitments
lead
substantial
variation
patterns
both
within
individuals.
Somatic
mutations
obtained
microdissected
biopsies
used
these
back
zygote.
Nature,
Journal Year:
2022,
Volume and Issue:
606(7913), P. 343 - 350
Published: June 1, 2022
Abstract
Age-related
change
in
human
haematopoiesis
causes
reduced
regenerative
capacity
1
,
cytopenias
2
immune
dysfunction
3
and
increased
risk
of
blood
cancer
4–6
but
the
reason
for
such
abrupt
functional
decline
after
70
years
age
remains
unclear.
Here
we
sequenced
3,579
genomes
from
single
cell-derived
colonies
haematopoietic
cells
across
10
subjects
0
to
81
age.
Haematopoietic
stem
or
multipotent
progenitors
(HSC/MPPs)
accumulated
a
mean
17
mutations
per
year
birth
lost
30
base
pairs
telomere
length.
Haematopoiesis
adults
less
than
65
was
massively
polyclonal,
with
high
clonal
diversity
stable
population
20,000–200,000
HSC/MPPs
contributing
evenly
production.
By
contrast,
individuals
aged
over
75
showed
profoundly
decreased
diversity.
In
each
older
subjects,
30–60%
accounted
by
12–18
independent
clones,
1–34%
Most
clones
had
begun
their
expansion
before
subject
40
old,
only
22%
known
driver
mutations.
Genome-wide
selection
analysis
estimated
that
between
34
12
non-synonymous
were
drivers,
accruing
at
constant
rates
throughout
life,
affecting
more
genes
identified
cancers.
Loss
Y
chromosome
conferred
selective
benefits
males.
Simulations
haematopoiesis,
cell
size
acquisition
conferring
moderate
fitness
benefits,
entirely
explained
structure
elderly.
Rapidly
decreasing
is
universal
feature
humans,
underpinned
pervasive
positive
acting
on
many
currently
identified.
Journal of Hematology & Oncology,
Journal Year:
2021,
Volume and Issue:
14(1)
Published: June 25, 2021
Tumors
are
not
only
aggregates
of
malignant
cells
but
also
well-organized
complex
ecosystems.
The
immunological
components
within
tumors,
termed
the
tumor
immune
microenvironment
(TIME),
have
long
been
shown
to
be
strongly
related
development,
recurrence
and
metastasis.
However,
conventional
studies
that
underestimate
potential
value
spatial
architecture
TIME
unable
completely
elucidate
its
complexity.
As
innovative
high-flux
high-dimensional
technologies
emerge,
researchers
can
more
feasibly
accurately
detect
depict
TIME.
These
findings
improved
our
understanding
complexity
role
in
biology.
In
this
review,
we
first
epitomized
some
representative
emerging
study
categorized
description
methods
used
characterize
these
structures.
Then,
determined
functions
biology
effects
gradient
extracellular
nonspecific
chemicals
(ENSCs)
on
We
discussed
clinical
architectures
TIME,
as
well
current
limitations
future
prospects
novel
field.
This
review
will
bring
an
dimension
ecosystem
research,
attention
promote
application
research
practice.
Science,
Journal Year:
2020,
Volume and Issue:
370(6512), P. 75 - 82
Published: Oct. 2, 2020
Genetic
profiles
of
the
bladder
Depending
on
environment
individual,
human
can
be
exposed
to
carcinogens
as
they
are
flushed
through
body.
Lawson
et
al.
and
Li
examined
genetic
composition
laser-dissected
microbiopsies
from
normal
cancer
cells
collected
urothelium,
a
specialized
epithelium
lining
lower
urinary
tract
(see
Perspective
by
Rozen).
These
complementary
studies
identified
mutational
landscape
urothelium
various
sequencing
strategies
high
heterogeneity
within
between
individuals
tumors.
Both
related
specific
such
aristolochic
acid
molecules
found
in
tobacco.
present
comprehensive
description
diverse
health
disease,
unraveling
positive
selection
for
cancer-causing
mutations,
diversity
processes,
large
differences
across
individuals.
Science
,
this
issue
p.
75
82
;
see
also
34
British Journal of Cancer,
Journal Year:
2021,
Volume and Issue:
124(11), P. 1759 - 1776
Published: March 29, 2021
Abstract
Cancer
is
a
leading
cause
of
death
worldwide
and,
despite
new
targeted
therapies
and
immunotherapies,
many
patients
with
advanced-stage-
or
high-risk
cancers
still
die,
owing
to
metastatic
disease.
Adoptive
T-cell
therapy,
involving
the
autologous
allogeneic
transplant
tumour-infiltrating
lymphocytes
genetically
modified
T
cells
expressing
novel
receptors
chimeric
antigen
receptors,
has
shown
promise
in
treatment
cancer
patients,
durable
responses
some
cases,
cure.
Technological
advances
genomics,
computational
biology,
immunology
cell
manufacturing
have
brought
aspiration
individualised
for
closer
reality.
This
era
cell-based
therapeutics
challenges
traditional
standards
therapeutic
interventions
provides
opportunities
paradigm
shift
our
approach
therapy.
Invited
speakers
at
2020
symposium
discussed
three
areas—cancer
cell-therapy
manufacturing—that
are
essential
effective
translation
solid
malignancies.
Key
been
made
understanding
genetic
intratumour
heterogeneity,
strategies
accurately
identify
neoantigens,
overcome
exhaustion
circumvent
tumour
immunosuppression
after
infusion
being
developed.
Advances
cell-manufacturing
approaches
that
potential
establish
cell-therapies
as
credible
options.
face
but
hold
great
improving
clinical
outcomes
tumours.
