Vincenzo Rallo
Researcher
Area of interest:
My expertise focuses on the analysis of genomic and transcriptomic data (WGS, WES, RNA seq and Single cell Seq). In recent years, I have structured and validated bioinformatics pipelines including database/dataset querying and optimization and automation of complex workflows for the identification of causal and/or predisposing variants to Mendelian disorders, complex diseases and related traits. Scientific interests have focused on multi-omics approaches and systematic statistical analysis integrating large datasets for the study of immunophenotypes involved in complex diseases. Recently, I am interested in investigating the spatial and temporal inter- and intra-tumoral heterogeneity by dissecting the cancer tissues into their cellular subpopulations.
Most significant publications:
2024
Serra, Rita; Rallo, Vincenzo; Steri, Maristella; Olla, Stefania; Piras, Maria Grazia; Marongiu, Michele; Gorospe, Myriam; Schlessinger, David; Pinna, Antonio; Fiorillo, Edoardo; Cucca, Francesco; Angius, Andrea
A large-scale screening identified in USH2A gene the P3272L founder pathogenic variant explaining familial Usher syndrome in Sardinia, Italy Journal Article
In: BMC Ophthalmol., 24 (1), pp. 306, 2024.
@article{Serra2024-gb,
title = {A large-scale screening identified in USH2A gene the P3272L founder pathogenic variant explaining familial Usher syndrome in Sardinia, Italy},
author = {Rita Serra and Vincenzo Rallo and Maristella Steri and Stefania Olla and Maria Grazia Piras and Michele Marongiu and Myriam Gorospe and David Schlessinger and Antonio Pinna and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},
year = {2024},
date = {2024-07-01},
urldate = {2024-07-01},
journal = {BMC Ophthalmol.},
volume = {24},
number = {1},
pages = {306},
publisher = {Springer Science and Business Media LLC},
abstract = {BACKGROUND: Usher syndrome (USH) encompasses a group of
disorders characterized by congenital sensorineural hearing loss
(SNHL) and retinitis pigmentosa (RP). We described the clinical
findings, natural history, and molecular analyses of USH
patients identified during a large-scale screening to identify
quantitative traits related to ocular disorders in the SardiNIA
project cohort. METHODS: We identified 3 USH-affected families
out of a cohort of 6,148 healthy subjects. 9 subjects presented
a pathological phenotype, with SNHL and RP. All patients and
their family members underwent a complete ophthalmic examination
including best-corrected visual acuity, slit-lamp biomicroscopy,
fundoscopy, fundus autofluorescence, spectral-domain optical
coherence tomography, and electrophysiological testing.
Audiological evaluation was performed with a clinical
audiometer. Genotyping was performed using several arrays
integrated with whole genome sequence data providing
approximately 22 million markers equally distributed for each
subject analyzed. Molecular diagnostics focused on analysis of
the following candidate genes: MYO7A, USH1C, CDH23, PCDH15,
USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A
single missense causal variant in USH2A gene was identified in
homozygous status in all patients and in heterozygous status in
unaffected parents. The presence of multiple homozygous patients
with the same phenotypic severity of the syndromic form suggests
that the Sardinian USH phenotype is the result of a founder
effect on a specific pathogenic variant related haplotype. The
frequency of heterozygotes in general Sardinian population is
1.89. Additionally, to provide new insights into the structure
of usherin and the pathological mechanisms caused by small
pathogenic in-frame variants, like p.Pro3272Leu, molecular
dynamics simulations of native and mutant protein-protein and
protein-ligand complexes were performed that predicted a
destabilization of the protein with a decrease in the free
energy change. CONCLUSIONS: Our results suggest that our
approach is effective for the genetic diagnosis of USH. Based on
the heterozygous frequency, targeted screening of this variant
in the general population and in families at risk or with
familial USH can be suggested. This can lead to more accurate
molecular diagnosis, better genetic counseling, and improved
molecular epidemiology data that are critical for future
intervention plans. TRIAL REGISTRATION: We did not perform any
health-related interventions for the participants.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Usher syndrome (USH) encompasses a group of
disorders characterized by congenital sensorineural hearing loss
(SNHL) and retinitis pigmentosa (RP). We described the clinical
findings, natural history, and molecular analyses of USH
patients identified during a large-scale screening to identify
quantitative traits related to ocular disorders in the SardiNIA
project cohort. METHODS: We identified 3 USH-affected families
out of a cohort of 6,148 healthy subjects. 9 subjects presented
a pathological phenotype, with SNHL and RP. All patients and
their family members underwent a complete ophthalmic examination
including best-corrected visual acuity, slit-lamp biomicroscopy,
fundoscopy, fundus autofluorescence, spectral-domain optical
coherence tomography, and electrophysiological testing.
Audiological evaluation was performed with a clinical
audiometer. Genotyping was performed using several arrays
integrated with whole genome sequence data providing
approximately 22 million markers equally distributed for each
subject analyzed. Molecular diagnostics focused on analysis of
the following candidate genes: MYO7A, USH1C, CDH23, PCDH15,
USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A
single missense causal variant in USH2A gene was identified in
homozygous status in all patients and in heterozygous status in
unaffected parents. The presence of multiple homozygous patients
with the same phenotypic severity of the syndromic form suggests
that the Sardinian USH phenotype is the result of a founder
effect on a specific pathogenic variant related haplotype. The
frequency of heterozygotes in general Sardinian population is
1.89. Additionally, to provide new insights into the structure
of usherin and the pathological mechanisms caused by small
pathogenic in-frame variants, like p.Pro3272Leu, molecular
dynamics simulations of native and mutant protein-protein and
protein-ligand complexes were performed that predicted a
destabilization of the protein with a decrease in the free
energy change. CONCLUSIONS: Our results suggest that our
approach is effective for the genetic diagnosis of USH. Based on
the heterozygous frequency, targeted screening of this variant
in the general population and in families at risk or with
familial USH can be suggested. This can lead to more accurate
molecular diagnosis, better genetic counseling, and improved
molecular epidemiology data that are critical for future
intervention plans. TRIAL REGISTRATION: We did not perform any
health-related interventions for the participants.
disorders characterized by congenital sensorineural hearing loss
(SNHL) and retinitis pigmentosa (RP). We described the clinical
findings, natural history, and molecular analyses of USH
patients identified during a large-scale screening to identify
quantitative traits related to ocular disorders in the SardiNIA
project cohort. METHODS: We identified 3 USH-affected families
out of a cohort of 6,148 healthy subjects. 9 subjects presented
a pathological phenotype, with SNHL and RP. All patients and
their family members underwent a complete ophthalmic examination
including best-corrected visual acuity, slit-lamp biomicroscopy,
fundoscopy, fundus autofluorescence, spectral-domain optical
coherence tomography, and electrophysiological testing.
Audiological evaluation was performed with a clinical
audiometer. Genotyping was performed using several arrays
integrated with whole genome sequence data providing
approximately 22 million markers equally distributed for each
subject analyzed. Molecular diagnostics focused on analysis of
the following candidate genes: MYO7A, USH1C, CDH23, PCDH15,
USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A
single missense causal variant in USH2A gene was identified in
homozygous status in all patients and in heterozygous status in
unaffected parents. The presence of multiple homozygous patients
with the same phenotypic severity of the syndromic form suggests
that the Sardinian USH phenotype is the result of a founder
effect on a specific pathogenic variant related haplotype. The
frequency of heterozygotes in general Sardinian population is
1.89. Additionally, to provide new insights into the structure
of usherin and the pathological mechanisms caused by small
pathogenic in-frame variants, like p.Pro3272Leu, molecular
dynamics simulations of native and mutant protein-protein and
protein-ligand complexes were performed that predicted a
destabilization of the protein with a decrease in the free
energy change. CONCLUSIONS: Our results suggest that our
approach is effective for the genetic diagnosis of USH. Based on
the heterozygous frequency, targeted screening of this variant
in the general population and in families at risk or with
familial USH can be suggested. This can lead to more accurate
molecular diagnosis, better genetic counseling, and improved
molecular epidemiology data that are critical for future
intervention plans. TRIAL REGISTRATION: We did not perform any
health-related interventions for the participants.
2023
Örr`u, Sandra; Pascariello, Emanuele; Pes, Barbara; Rallo, Vincenzo; Barbara, Raffaele; Muntoni, Marta; Notari, Francesca; Fancello, Gianfranco; Mocci, Cristina; Muroni, Maria Rosaria; Cossu-Rocca, Paolo; Angius, Andrea; Miglio, Maria Rosaria" De
Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype Journal Article
In: Sci. Rep., 13 (1), pp. 12869, 2023.
@article{Orru2023-vp,
title = {Biomarker dynamics affecting neoadjuvant therapy response and
outcome of HER2-positive breast cancer subtype},
author = {Sandra Örr`u and Emanuele Pascariello and Barbara Pes and Vincenzo Rallo and Raffaele Barbara and Marta Muntoni and Francesca Notari and Gianfranco Fancello and Cristina Mocci and Maria Rosaria Muroni and Paolo Cossu-Rocca and Andrea Angius and Maria Rosaria" De Miglio},
year = {2023},
date = {2023-08-01},
journal = {Sci. Rep.},
volume = {13},
number = {1},
pages = {12869},
publisher = {Springer Science and Business Media LLC},
abstract = {HER2+ breast cancer (BC) is an aggressive subtype genetically
and biologically heterogeneous. We evaluate the predictive and
prognostic role of HER2 protein/gene expression levels combined
with clinico-pathologic features in 154 HER2+ BCs patients who
received trastuzumab-based neoadjuvant chemotherapy (NACT). The
tumoral pathological complete response (pCR) rate was 40.9%.
High tumoral pCR show a scarce mortality rate vs subjects with a
lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were
HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the
remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with
a high percentage of infiltrating immune cells and right-sided
tumors, that reduce distant metastasis and improve survival, but
no incidence difference. HER2 IHC score and laterality emerge as
strong predictors of tumoral pCR after NACT from machine
learning analysis. HER2 IHC3+ and G3 are poor prognostic factors
for HER2+ BC patients, and could be considered in the
application of neoadjuvant therapy. Increasing TILs
concentrations, lower lymph node ratio and lower residual tumor
cellularity are associated with a better outcome. The immune
microenvironment and scarce lymph node involvement have crucial
role in clinical outcomes. The combination of all predictors
might offer new options for NACT effectiveness prediction and
stratification of HER2+ BC during clinical decision-making.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
HER2+ breast cancer (BC) is an aggressive subtype genetically
and biologically heterogeneous. We evaluate the predictive and
prognostic role of HER2 protein/gene expression levels combined
with clinico-pathologic features in 154 HER2+ BCs patients who
received trastuzumab-based neoadjuvant chemotherapy (NACT). The
tumoral pathological complete response (pCR) rate was 40.9%.
High tumoral pCR show a scarce mortality rate vs subjects with a
lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were
HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the
remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with
a high percentage of infiltrating immune cells and right-sided
tumors, that reduce distant metastasis and improve survival, but
no incidence difference. HER2 IHC score and laterality emerge as
strong predictors of tumoral pCR after NACT from machine
learning analysis. HER2 IHC3+ and G3 are poor prognostic factors
for HER2+ BC patients, and could be considered in the
application of neoadjuvant therapy. Increasing TILs
concentrations, lower lymph node ratio and lower residual tumor
cellularity are associated with a better outcome. The immune
microenvironment and scarce lymph node involvement have crucial
role in clinical outcomes. The combination of all predictors
might offer new options for NACT effectiveness prediction and
stratification of HER2+ BC during clinical decision-making.
and biologically heterogeneous. We evaluate the predictive and
prognostic role of HER2 protein/gene expression levels combined
with clinico-pathologic features in 154 HER2+ BCs patients who
received trastuzumab-based neoadjuvant chemotherapy (NACT). The
tumoral pathological complete response (pCR) rate was 40.9%.
High tumoral pCR show a scarce mortality rate vs subjects with a
lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were
HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the
remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with
a high percentage of infiltrating immune cells and right-sided
tumors, that reduce distant metastasis and improve survival, but
no incidence difference. HER2 IHC score and laterality emerge as
strong predictors of tumoral pCR after NACT from machine
learning analysis. HER2 IHC3+ and G3 are poor prognostic factors
for HER2+ BC patients, and could be considered in the
application of neoadjuvant therapy. Increasing TILs
concentrations, lower lymph node ratio and lower residual tumor
cellularity are associated with a better outcome. The immune
microenvironment and scarce lymph node involvement have crucial
role in clinical outcomes. The combination of all predictors
might offer new options for NACT effectiveness prediction and
stratification of HER2+ BC during clinical decision-making.
Serra, Rita; Rallo, Vincenzo; Pinna, Antonio; Steri, Maristella; Piras, Maria Grazia; Marongiu, Michele; Coscas, Florence; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Cucca, Francesco; Angius, Andrea
Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia Journal Article
In: Ärbeitsphysiologie", 261 (3), pp. 691–698, 2023.
@article{Serra2023-ve,
title = {Polygenic risk score and biochemical/environmental variables
predict a low-risk profile of age-related macular degeneration
in Sardinia},
author = {Rita Serra and Vincenzo Rallo and Antonio Pinna and Maristella Steri and Maria Grazia Piras and Michele Marongiu and Florence Coscas and Myriam Gorospe and David Schlessinger and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},
year = {2023},
date = {2023-03-01},
journal = {Ärbeitsphysiologie"},
volume = {261},
number = {3},
pages = {691--698},
publisher = {Springer Science and Business Media LLC},
abstract = {PURPOSE: To ascertain the prevalence and clinical and genetic
features of age-related macular degeneration (AMD) in subjects
living in the Lanusei valley, Central Sardinia, Italy, involved
in a study on ageing (SardiNIA project). METHODS: A total of 814
volunteers aged $geq$ 50 years, randomly selected from the
SardiNIA project dataset, were included. A color fundus (CF)
photograph of the 30° central retina of each eye was obtained
and graded according to the Age-Related Eye Disease Study
system. Life-style choices were investigated using standardized
questionnaires. The concentrations of several inflammatory
biomarkers (i.e., complement component, fibrinogen, and
C-reactive protein) were measured. Polygenic risk score (PRS)
was calculated and compared with results obtained from a
European cohort. RESULTS: A total of 756 subjects had gradable
CF photographs for AMD detection. In 91.3%, no signs of AMD
were observed. The prevalence rates of early and late AMDs were
6.9% and 0.6%, respectively. A total of 85% of subjects were
physically active; only 13.5% were current smokers. Low
concentrations of complement component, fibrinogen, and
C-reactive protein were found. We calculated the polygenic risk
scores (PRS) using 40 AMD markers distributed on several
candidate genes in Europeans and Sardinians. The mean PRS value
was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectivel},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: To ascertain the prevalence and clinical and genetic
features of age-related macular degeneration (AMD) in subjects
living in the Lanusei valley, Central Sardinia, Italy, involved
in a study on ageing (SardiNIA project). METHODS: A total of 814
volunteers aged $geq$ 50 years, randomly selected from the
SardiNIA project dataset, were included. A color fundus (CF)
photograph of the 30° central retina of each eye was obtained
and graded according to the Age-Related Eye Disease Study
system. Life-style choices were investigated using standardized
questionnaires. The concentrations of several inflammatory
biomarkers (i.e., complement component, fibrinogen, and
C-reactive protein) were measured. Polygenic risk score (PRS)
was calculated and compared with results obtained from a
European cohort. RESULTS: A total of 756 subjects had gradable
CF photographs for AMD detection. In 91.3%, no signs of AMD
were observed. The prevalence rates of early and late AMDs were
6.9% and 0.6%, respectively. A total of 85% of subjects were
physically active; only 13.5% were current smokers. Low
concentrations of complement component, fibrinogen, and
C-reactive protein were found. We calculated the polygenic risk
scores (PRS) using 40 AMD markers distributed on several
candidate genes in Europeans and Sardinians. The mean PRS value
was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectivel
features of age-related macular degeneration (AMD) in subjects
living in the Lanusei valley, Central Sardinia, Italy, involved
in a study on ageing (SardiNIA project). METHODS: A total of 814
volunteers aged $geq$ 50 years, randomly selected from the
SardiNIA project dataset, were included. A color fundus (CF)
photograph of the 30° central retina of each eye was obtained
and graded according to the Age-Related Eye Disease Study
system. Life-style choices were investigated using standardized
questionnaires. The concentrations of several inflammatory
biomarkers (i.e., complement component, fibrinogen, and
C-reactive protein) were measured. Polygenic risk score (PRS)
was calculated and compared with results obtained from a
European cohort. RESULTS: A total of 756 subjects had gradable
CF photographs for AMD detection. In 91.3%, no signs of AMD
were observed. The prevalence rates of early and late AMDs were
6.9% and 0.6%, respectively. A total of 85% of subjects were
physically active; only 13.5% were current smokers. Low
concentrations of complement component, fibrinogen, and
C-reactive protein were found. We calculated the polygenic risk
scores (PRS) using 40 AMD markers distributed on several
candidate genes in Europeans and Sardinians. The mean PRS value
was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectivel
2021
Ängius, Andrea; Scanu, Antonio Mario; Arru, Caterina; Muroni, Maria Rosaria; Rallo, Vincenzo; Deiana, Giulia; Ninniri, Maria Chiara; Carru, Ciriaco; Porcu, Alberto; Pira, Giovanna; Uva, Paolo; Cossu-Rocca, Paolo; Miglio, Maria Rosaria" De
Portrait of cancer stem cells on colorectal cancer: Molecular biomarkers, signaling pathways and miRNAome Journal Article
In: Int. J. Mol. Sci., 22 (4), pp. 1603, 2021.
@article{Angius2021-bx,
title = {Portrait of cancer stem cells on colorectal cancer: Molecular
biomarkers, signaling pathways and miRNAome},
author = {Andrea Ängius and Antonio Mario Scanu and Caterina Arru and Maria Rosaria Muroni and Vincenzo Rallo and Giulia Deiana and Maria Chiara Ninniri and Ciriaco Carru and Alberto Porcu and Giovanna Pira and Paolo Uva and Paolo Cossu-Rocca and Maria Rosaria" De Miglio},
year = {2021},
date = {2021-02-01},
journal = {Int. J. Mol. Sci.},
volume = {22},
number = {4},
pages = {1603},
publisher = {MDPI AG},
abstract = {Colorectal cancer (CRC) is a leading cause of cancer death
worldwide, and about 20% is metastatic at diagnosis and
untreatable. Increasing evidence suggests that the heterogeneous
nature of CRC is related to colorectal cancer stem cells
(CCSCs), a small cells population with stemness behaviors and
responsible for tumor progression, recurrence, and therapy
resistance. Growing knowledge of stem cells (SCs) biology has
rapidly improved uncovering the molecular mechanisms and
possible crosstalk/feedback loops between signaling pathways
that directly influence intestinal homeostasis and
tumorigenesis. The generation of CCSCs is probably connected to
genetic changes in members of signaling pathways, which control
self-renewal and pluripotency in SCs and then establish function
and phenotype of CCSCs. Particularly, various deregulated
CCSC-related miRNAs have been reported to modulate stemness
features, controlling CCSCs functions such as regulation of cell
cycle genes expression, epithelial-mesenchymal transition,
metastasization, and drug-resistance mechanisms. Primarily,
CCSC-related miRNAs work by regulating mainly signal pathways
known to be involved in CCSCs biology. This review intends to
summarize the epigenetic findings linked to miRNAome in the
maintenance and regulation of CCSCs, including their
relationships with different signaling pathways, which should
help to identify specific diagnostic, prognostic, and predictive
biomarkers for CRC, but also develop innovative CCSCs-targeted
therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Colorectal cancer (CRC) is a leading cause of cancer death
worldwide, and about 20% is metastatic at diagnosis and
untreatable. Increasing evidence suggests that the heterogeneous
nature of CRC is related to colorectal cancer stem cells
(CCSCs), a small cells population with stemness behaviors and
responsible for tumor progression, recurrence, and therapy
resistance. Growing knowledge of stem cells (SCs) biology has
rapidly improved uncovering the molecular mechanisms and
possible crosstalk/feedback loops between signaling pathways
that directly influence intestinal homeostasis and
tumorigenesis. The generation of CCSCs is probably connected to
genetic changes in members of signaling pathways, which control
self-renewal and pluripotency in SCs and then establish function
and phenotype of CCSCs. Particularly, various deregulated
CCSC-related miRNAs have been reported to modulate stemness
features, controlling CCSCs functions such as regulation of cell
cycle genes expression, epithelial-mesenchymal transition,
metastasization, and drug-resistance mechanisms. Primarily,
CCSC-related miRNAs work by regulating mainly signal pathways
known to be involved in CCSCs biology. This review intends to
summarize the epigenetic findings linked to miRNAome in the
maintenance and regulation of CCSCs, including their
relationships with different signaling pathways, which should
help to identify specific diagnostic, prognostic, and predictive
biomarkers for CRC, but also develop innovative CCSCs-targeted
therapies.
worldwide, and about 20% is metastatic at diagnosis and
untreatable. Increasing evidence suggests that the heterogeneous
nature of CRC is related to colorectal cancer stem cells
(CCSCs), a small cells population with stemness behaviors and
responsible for tumor progression, recurrence, and therapy
resistance. Growing knowledge of stem cells (SCs) biology has
rapidly improved uncovering the molecular mechanisms and
possible crosstalk/feedback loops between signaling pathways
that directly influence intestinal homeostasis and
tumorigenesis. The generation of CCSCs is probably connected to
genetic changes in members of signaling pathways, which control
self-renewal and pluripotency in SCs and then establish function
and phenotype of CCSCs. Particularly, various deregulated
CCSC-related miRNAs have been reported to modulate stemness
features, controlling CCSCs functions such as regulation of cell
cycle genes expression, epithelial-mesenchymal transition,
metastasization, and drug-resistance mechanisms. Primarily,
CCSC-related miRNAs work by regulating mainly signal pathways
known to be involved in CCSCs biology. This review intends to
summarize the epigenetic findings linked to miRNAome in the
maintenance and regulation of CCSCs, including their
relationships with different signaling pathways, which should
help to identify specific diagnostic, prognostic, and predictive
biomarkers for CRC, but also develop innovative CCSCs-targeted
therapies.
2019
Balzano, Francesca; Campesi, Ilaria; Cruciani, Sara; Garroni, Giuseppe; Bellu, Emanuela; Giudici, Silvia Dei; Angius, Andrea; Oggiano, Annalisa; Rallo, Vincenzo; Capobianco, Giampiero; Dessole, Salvatore; Ventura, Carlo; Montella, Andrea; Maioli, Margherita
Epigenetics, stem cells, and autophagy: Exploring a path involving miRNA Journal Article
In: Int. J. Mol. Sci., 20 (20), pp. 5091, 2019.
@article{Balzano2019-fl,
title = {Epigenetics, stem cells, and autophagy: Exploring a path
involving miRNA},
author = {Francesca Balzano and Ilaria Campesi and Sara Cruciani and Giuseppe Garroni and Emanuela Bellu and Silvia Dei Giudici and Andrea Angius and Annalisa Oggiano and Vincenzo Rallo and Giampiero Capobianco and Salvatore Dessole and Carlo Ventura and Andrea Montella and Margherita Maioli},
year = {2019},
date = {2019-10-01},
journal = {Int. J. Mol. Sci.},
volume = {20},
number = {20},
pages = {5091},
publisher = {MDPI AG},
abstract = {MiRNAs, a small family of non-coding RNA, are now emerging as
regulators of stem cell pluripotency, differentiation, and
autophagy, thus controlling stem cell behavior. Stem cells are
undifferentiated elements capable to acquire specific phenotype
under different kind of stimuli, being a main tool for
regenerative medicine. Within this context, we have previously
shown that stem cells isolated from Wharton jelly multipotent
stem cells (WJ-MSCs) exhibit gender differences in the
expression of the stemness related gene OCT4 and the epigenetic
modulator gene DNA-Methyltransferase (DNMT1). Here, we further
analyze this gender difference, evaluating adipogenic and
osteogenic differentiation potential, autophagic process, and
expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived
from males and females. These miRNAs were selected since they
are involved in OCT4 and DNMT1 gene expression, and in stem cell
differentiation. Our results indicate a difference in the
regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in
male WJ-MSCs as compared to female cells. Moreover, no
difference was detected in the expression of the
two-differentiation regulating miRNA (miR-145 and miR-185).
Taken together, our results highlight a different behavior of
WJ-MSCs from males and females, disclosing the chance to better
understand cellular processes as autophagy and stemness, usable
for future clinical applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
MiRNAs, a small family of non-coding RNA, are now emerging as
regulators of stem cell pluripotency, differentiation, and
autophagy, thus controlling stem cell behavior. Stem cells are
undifferentiated elements capable to acquire specific phenotype
under different kind of stimuli, being a main tool for
regenerative medicine. Within this context, we have previously
shown that stem cells isolated from Wharton jelly multipotent
stem cells (WJ-MSCs) exhibit gender differences in the
expression of the stemness related gene OCT4 and the epigenetic
modulator gene DNA-Methyltransferase (DNMT1). Here, we further
analyze this gender difference, evaluating adipogenic and
osteogenic differentiation potential, autophagic process, and
expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived
from males and females. These miRNAs were selected since they
are involved in OCT4 and DNMT1 gene expression, and in stem cell
differentiation. Our results indicate a difference in the
regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in
male WJ-MSCs as compared to female cells. Moreover, no
difference was detected in the expression of the
two-differentiation regulating miRNA (miR-145 and miR-185).
Taken together, our results highlight a different behavior of
WJ-MSCs from males and females, disclosing the chance to better
understand cellular processes as autophagy and stemness, usable
for future clinical applications.
regulators of stem cell pluripotency, differentiation, and
autophagy, thus controlling stem cell behavior. Stem cells are
undifferentiated elements capable to acquire specific phenotype
under different kind of stimuli, being a main tool for
regenerative medicine. Within this context, we have previously
shown that stem cells isolated from Wharton jelly multipotent
stem cells (WJ-MSCs) exhibit gender differences in the
expression of the stemness related gene OCT4 and the epigenetic
modulator gene DNA-Methyltransferase (DNMT1). Here, we further
analyze this gender difference, evaluating adipogenic and
osteogenic differentiation potential, autophagic process, and
expression of miR-145, miR-148a, and miR-185 in WJ-MSCs derived
from males and females. These miRNAs were selected since they
are involved in OCT4 and DNMT1 gene expression, and in stem cell
differentiation. Our results indicate a difference in the
regulatory circuit involving miR-148a/DNMT1/OCT4 autophagy in
male WJ-MSCs as compared to female cells. Moreover, no
difference was detected in the expression of the
two-differentiation regulating miRNA (miR-145 and miR-185).
Taken together, our results highlight a different behavior of
WJ-MSCs from males and females, disclosing the chance to better
understand cellular processes as autophagy and stemness, usable
for future clinical applications.
- Monserrato