
Antonio AdamoKing Abdullah University of Science and Technology | KAUST · Department of Bioscience
Antonio Adamo
Medical Biotechnologies and Molecular Medicine
About
30
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Introduction
We use hESCs and patient-derived iPSCs to model the onset and progression of human diseases linked to copy number variations “in a dish.” We developed the largest cohort of Klinefelter syndrome (karyotype 47,XXY) and high-grade X aneuploid iPSCs (karyotype 48,XXXY and 49,XXXXY) to study the molecular dysregulations linked to X aneuploidy. In our lab we combine reprogramming, organoid derivation, and genome editing to identify the transcriptional and epigenetic signatures of human diseases.
Publications
Publications (30)
Male sex chromosome aneuploidies are frequent genetic aberrations in humans characterized by additional Y or X chromosome complements. Jacob (JS) and Klinefelter syndromes (KS), carrying 47,XYY and 47,XXY chromosomes, respectively, share several clinical features, including sterility, hormonal deficits, neurocognitive delay, and skeletal-muscle def...
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a promising cell source for cardiac regenerative medicine and in vitro modeling. However, hPSC-CMs exhibit immature structural and functional properties compared with adult cardiomyocytes. Various electrical, mechanical, and biochemical cues have been applied to enhance hPSC-CM matur...
Somatic cell reprogramming allows the generation of human induced pluripotent stem cells (iPSCs) from patient’s cells. The derived iPSCs provide an unlimited source of patient-specific cells that can be virtually differentiated in any cell of the human body. The generation of iPSCs has important implications for all human medicine fields, as they c...
The derivation of cardiomyocytes from human pluripotent stem cells (hPSCs) is a powerful tool to investigate early cardiogenesis and model diseases in vitro. Here, we present an optimized protocol to obtain contracting hPSCs-derived cardiomyocytes using a ready-to-use kit. We describe steps for hPSC culture and differentiation to cardiomyocytes inc...
Objective:
The transcriptional landscape of Klinefelter syndrome during early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males iPSCs obtained from patients with different genomic background and ethnicity.
Design and method:
We derived and characterized 15 iPSC lines from four Saudi...
The histone demethylase KDM1A is a multi-faceted regulator of vital developmental processes, including mesodermal and cardiac tube formation during gastrulation. However, it is unknown whether the fine-tuning of KDM1A splicing isoforms, already shown to regulate neuronal maturation, is crucial for the specification and maintenance of cell identity...
Human pluripotent stem cells (hPSCs) constitute a valuable model to study the complexity of early human cardiac development and investigate the molecular mechanisms involved in heart diseases. The differentiation of hPSCs into cardiac lineages in vitro can be achieved by traditional two-dimensional (2D) monolayer approaches or by adopting innovativ...
Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by a 47,XXY karyotype. Less frequently, higher grade sex chromosome aneuploidies (HGAs) can also occur. Here, using a paradigmatic cohort of KS and HGA induced pluripotent stem cells (iPSCs) carrying 49,XXXXY, 48,XXXY, and 47,XXY karyotypes, we identified the g...
Lysine-specific demethylase 1 (LSD1/KDM1A) removes methylation of histone and non-histone substrates, and recruits a repressive chromatin complex. De novo LSD1 mutations impairing protein function lead to a rare neurodevelopmental disorder, but the molecular mechanisms of the pathology are unclear. Using patient-derived fibroblasts, reprogrammed pl...
Klinefelter Syndrome (KS) is the most common X chromosome aneuploidy in males characterized by highly heterogeneous clinical manifestations including a subtle cognitive impairment and multisystemic disorders such as infertility, metabolic syndrome, gynecomastia and cardiovascular diseases. To date dosage-dependent correlation studies of X-linked ge...
Klinefelter Syndrome (KS) is the most common aneuploidy in humans (prevalence: 85–250 per 100,000 born males) and is characterized by one or more supernumerary X-chromosomes (47-XXY, 48-XXXY and 49-XXXXY karyotypes). KS is a multisystemic disorder associated to multiple phenotypic features including cardiac abnormalities, infertility, mental retard...
Klinefelter Syndrome (KS) is caused by the presence of a supernumerary X chromosome. Cytogenetic studies revaled that 80–90% of patients carry a 47-XXY karyotype, while 10–20% of cases are represented by mosaic 46-XY/47-XXY and high-grade aneuploidies 48-XXXY and 48-XXYY. The phenotypic traits of KS are highly variable across individuals and includ...
While Klinefelter Syndrome (KS) has a prevalence of 85–250 per 100,000 born males, patients are typically underdiagnosed due to a subtle phenotype emerging only late during puberty or adulthood. Rare cases of KS carry a mosaic phenotype 47-XXY/46-XY associated to mild phenotypic traits mostly compatible with a normal life including preserved fertil...
Glucagon-like peptide-1 receptor (GLP1R) is a seven-transmembrane-spanning helices membrane protein expressed in multiple human tissues including pancreatic islets, lung, brain, heart and central nervous system (CNS). GLP1R agonists are commonly used as antidiabetic drugs, but a neuroprotective function in neurodegenerative disorders is emerging. H...
Klinefelter Syndrome (KS) is the most frequent X chromosome aneuploidy in males. KS patients with 47-XXY, 48-XXXY and 49-XXXXY karyotypes endure inter-individual phenotypic variabilities including infertility, cardiac diseases, metabolic and psychiatric disorders. We derived iPSC lines from a high-grade 49-XXXXY KS and two healthy donors' fibroblas...
Motivation: Leucine-aspartic acid (LD) motifs are short linear interaction motifs (SLiMs) that link paxillin family proteins to factors controlling cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood. Results: To enable a proteome-wide assessment of LD motifs, we developed...
Motivation:
Leucine-aspartic acid (LD) motifs are short linear interaction motifs (SLiMs) that link paxillin family proteins to factors controlling cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood.
Results:
To enable a proteome-wide assessment of LD motifs, we develop...
The raising worldwide prevalence of Type 1 and Type 2 diabetes mellitus (T1DM and T2DM) solicits the derivation of in vitro methods yielding mature and fully functional β-cells to be used in regenerative medicine. Several protocols to differentiate human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into human pancreatic β...
RNA sequencing (RNAseq) has become the method of choice for transcriptome analysis, yet no consensus exists as to the most
appropriate pipeline for its analysis, with current benchmarks suffering important limitations. Here, we address these challenges
through a rich benchmarking resource harnessing (i) two RNAseq datasets including ERCC ExFold spi...
Cell reprogramming promises to make characterization of the impact of human genetic variation on health and disease experimentally tractable by enabling the bridging of genotypes to phenotypes in developmentally relevant human cell lineages. Here we apply this paradigm to two disorders caused by symmetrical copy number variations of 7q11.23, which...
The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific
sets of transcription factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133+ cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNC...
The pig represents an ideal large-animal model, intermediate between rodents and humans, for the preclinical assessment of emerging cell therapies. As no validated pig embryonic stem (pES) cell lines have been derived so far, pig induced pluripotent stem cells (piPSCs) should offer an alternative source of undifferentiated cells to advance regenera...
2350
The finding that the epigenome of differentiated cells can be reset to a pluripotent state indicates that any somatic cell may potentially change or reverse its already established developmental identity through the delivery of appropriate instructive signals. Here we show the possibility of generating mature and functional neurons from Cord B...
Comment on: Adamo A, et al. Nat Cell Biol 2011; 13:652-60.
We identify LSD1 (lysine-specific demethylase 1; also known as KDM1A and AOF2) as a key histone modifier that participates in the maintenance of pluripotency through the regulation of bivalent domains, a chromatin environment present at the regulatory regions of developmental genes that contains both H3K4 di/trimethylation and H3K27 trimethylation...
A variety of chromatin remodeling complexes are thought to orchestrate transcriptional programs that lead neuronal precursors from earliest commitment to terminal differentiation. Here we show that mammalian neurons have a specialized chromatin remodeling enzyme arising from a neurospecific splice variant of LSD1/KDM1, histone lysine specific demet...
Histone demethylase LSD1 regulates transcription by demethylating Lys(4) of histone H3. The crystal structure of the enzyme in complex with CoREST and a substrate-like peptide inhibitor highlights an intricate network of interactions and a folded conformation of the bound peptide. The core of the peptide structure is formed by Arg(2), Gln(5), and S...