Iván Velasco

Iván Velasco
Universidad Nacional Autónoma de México | UNAM · Instituto de Fisiologia Celular-Neurociencias

About

64
Publications
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4,268
Citations
Additional affiliations
September 2000 - June 2003
National Institutes of Health
Position
  • PostDoc Position

Publications

Publications (64)
Article
Full-text available
Animal models are useful to study the molecular, cellular, and morphogenetic mechanisms underlying normal and pathological development. Cell-based study models have emerged as an alternative approach to study many aspects of human embryonic development and disease. The neural crest (NC) is a transient, multipotent, and migratory embryonic cell popu...
Article
Full-text available
The process of freezing cells or tissues and depositing them in liquid nitrogen at –196 °C is called cryopreservation. Sub-zero temperature is not a physiological condition for cells and water ice crystals represent the main problem since they induce cell death, principally in large cells like oocytes, which have a meiotic spindle that degenerates...
Article
Full-text available
Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profile...
Article
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Parkinson’s disease (PD) is characterized by the progressive loss of midbrain dopaminergic neurons (DaNs) of the substantia nigra pars compacta and the decrease of dopamine in the brain. Grafting DaN differentiated from embryonic stem cells (ESCs) has been proposed as an alternative therapy for current pharmacological treatments. Intrastriatal graf...
Article
Full-text available
A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripoten...
Article
Full-text available
Neural stem/progenitor cells (NSPC) are multipotent cells that renew themselves and could differentiate into neurons and macro glia (astrocytes and oligodendrocytes) of the nervous system during embryonic development. Duchenne muscular dystrophy is a severe type of muscular dystrophy caused by mutations in the dmd gene, and one-third of patients cu...
Article
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Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this...
Article
The neuromuscular junction (NMJ) is a specialized structure that works as an interface to translate the action potential of the presynaptic motor neuron (MN) in the contraction of the postsynaptic myofiber. The design of appropriate experimental models is essential to have efficient and reliable approaches to study NMJ development and function, but...
Preprint
Full-text available
Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DAN). Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson disease (PD) patients. We obtained DAN from hESCs and confirmed that they express dopaminergic mar...
Article
Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations in the dystrophin gene. Dystrophin is required for the organization of a complex consisting of dystroglycans, sarcoglycans, dystrobrevins and syntrophins, known as the dystrophin-associated proteins complex (DAPC). In addition to muscle degeneration, cognitive impairment has...
Article
Full-text available
The neural crest (NC) is a transient multipotent cell population that originates in the dorsal neural tube. Cells of the NC are highly migratory, as they travel considerable distances through the body to reach their final sites. Derivatives of the NC are neurons and glia of the peripheral nervous system and the enteric nervous system, as well as no...
Data
Figure 2: Contribution of neural crest cells to the formation of cranial nerves I, III, V, VII, VIII, IX, X, and XI. These selected cranial nerves are formed by the contribution of cranial placodes and neural crest cells, indicated in green. Neural crest-derived Schwann cells produce peripheral myelination of cranial nerves III-XII. The sensory ner...
Data
Figure 3. Gene regulatory network involved in neural crest contribution to the formation of cranial nerves. The cranial ganglia and cranial nerves are formed in precise positions along the dorso-ventral and antero-posterior axes of the midbrain/hindbrain region. (A) The drawing represents a human embryo at stage 13 (30 days, 32 somites), equivalent...
Data
Figure 1. Neural crest origin, regions in human and mouse embryos and some of its cranial derivatives. (A) The top-left part of the scheme shows the origin of the neural crest cells (green) that migrate through the embryo. On the top-right side, the level of axial origin (see axial color key) of different regions of the neural crest is represented...
Article
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During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic processes such as DNA methylation and demethylation as well as post-translational modification of histones occur during neurogenesis. Here, we administered histamine (HA) into the brain of E12 embryos in vivo and observed significant lower immunoreactivity...
Article
Neurological disorders are a public health problem worldwide for which there is currently no direct treatment of the cause of the disorder. The goal of this study was to investigate the potential in vitro neuroprotective property of plants used in Mayan traditional medicine. Plant ethanolic extracts were prepared and tested on models in which neuro...
Article
Full-text available
The neural crest (NC) comprises a multipotent cell population that produces peripheral neurons, cartilage, and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with cons...
Article
Full-text available
The neural crest (NC) comprises a multipotent cell population that produces peripheral neurons, cartilage, and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with cons...
Article
Full-text available
HoxA9 is an evolutionarily conserved homeobox gene implicated in embryo development. To study the roles of Hoxa9 during human development we generated a transgenic H9 (hESC) line that overexpresses HoxA9 and the Enhanced Green Fluorescent Protein (EGFP), and a control H9 with a stable expression of the EGFP. The resulting H9-HoxA9-EGFP and H9-EGFP...
Article
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Glial cell line-derived neurotrophic factor (GDNF) was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs). Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neur...
Article
Full-text available
Coenzyme Q10 (CoQ10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC), and is an essential antioxidant. Mutations in genes responsible for CoQ10 biosynthesis (COQ genes) cause primary CoQ10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype associ...
Article
Full-text available
Embryonic stem cells (ESC) are pluripotent and thus can differentiate into every cell type present in the body. Directed differentiation into motor neurons (MNs) has been described for pluripotent cells. Although neurotrophic factors promote neuronal survival, their role in neuronal commitment is elusive. Here, we developed double-transgenic lines...
Article
Full-text available
Cell therapy in experimental models of Parkinson Disease replaces the lost dopamine neurons (DAN), but we still need improved methods to guide dopaminergic axons of grafted neurons to make proper connections. The protein Semaphorin 3C (Sema3C) attracts dopamine neuron axons and enhances their growth. In this work we show that a hydrogel Puramatrix,...
Article
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Stem cell research is attracting wide attention as a promising and fast-growing field in Latin America, as it is worldwide. Many countries in the region have defined Regenerative Medicine as a research priority and a focus of investment. This field generates not only opportunities but also regulatory, technical and operative challenges. In this rev...
Article
Full-text available
Damage caused to neural tissue by disease or injury frequently produces a discontinuity in the nervous system (NS). Such damage generates diverse alterations that are commonly permanent, due to the limited regeneration capacity of the adult NS, particularly the Central Nervous System (CNS). The cellular reaction to noxious stimulus leads to several...
Article
Full-text available
Access to healthy or diseased human neural tissue is a daunting task and represents a barrier for advancing our understanding about the cellular, genetic, and molecular mechanisms underlying neurogenesis and neurodegeneration. Reprogramming of somatic cells to pluripotency by transient expression of transcription factors was achieved a few years ag...
Article
Full-text available
Cell therapy in animal models of Parkinson's disease (PD) is effective after intrastriatal grafting of dopamine (DA) neurons, whereas intranigral transplantation of dopaminergic cells does not cause consistent behavioral recovery. One strategy to promote axonal growth of dopaminergic neurons from the substantia nigra (SN) to the striatum is degrada...
Article
Full-text available
Background During rat development, histamine (HA) is one of the first neuroactive molecules to appear in the brain, reaching its maximal value at embryonic day 14, a period when neurogenesis of deep layers is occurring in the cerebral cortex, suggesting a role of this amine in neuronal specification. We previously reported, using high-density cereb...
Article
Transforming Growth Factor-β (TGF-β) family members are ubiquitously expressed, participating in the regulation of many processes in different cell types both in embryonic and adult stages. Several members of this family, including Activins, TGF-β1-3 and Nodal, have been implicated in the development and maintenance of various organs, in which stem...
Article
Full-text available
Activin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective, but its role in brain development is still elusive. We studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin...
Article
Histamine in the adult central nervous system (CNS) acts as a neurotransmitter. This amine is one of the first neurotransmitters to appear during development reaching its maximum concentration simultaneously with neuron differentiation peak. This suggests that HA plays an important role in neurogenesis. We have previously shown that HA is able to i...
Article
Embryonic stem (ES) cells have the capacity to differentiate into endodermal, mesodermal, and ectodermal lineages. Motor neuron (MN) differentiation of mouse ES cells involves embryoid bodies formation with addition of Sonic hedgehog and retinoic acid. In this work, using immunocytochemistry, flow cytometry, and quantitative RT-PCR, we investigated...
Article
Full-text available
Chemotropic proteins guide neuronal projections to their final target during embryo development and are useful to guide axons of neurons used in transplantation therapies. Site-specific delivery of the proteins however is needed for their application in the brain to avoid degradation and pleiotropic affects. In the present study we report the use o...
Article
Bioactive lipids serve as intracellular and extracellular mediators in cell signaling in normal and pathological conditions. Here we describe that an important regulator of some of these lipids, the lipid phosphate phosphatase-3 (LPP3), is abundantly expressed in specific plasma membrane domains of Bergmann glia (BG), a specialized type of astrocyt...
Article
Pluripotent and multipotent stem cells with differentiation potential to neural phenotypes have been described and characterized in the last decades. Embryonic stem cells, as well as neural stem cells from developing and adult nervous system, can differentiate into different types of neurons, astrocytes or oligodendrocytes. Although the initially i...
Article
Embryonic stem (ES) cells can be induced to differentiate into motor neurons (MN). Animal models resembling MN degeneration and paralysis observed in familial amyotrophic lateral sclerosis (ALS) have been previously reported. In this work, we aimed to investigate whether transplanted MN could prevent motor deterioration in transgenic rats expressin...
Article
Progesterone participates in the regulation of several functions in mammals, including brain differentiation and dopaminergic transmission, but the role of progesterone in dopaminergic cell differentiation is unknown. We investigated the effects of progesterone on dopaminergic differentiation of embryonic stem cells using a five-stage protocol. Cel...
Article
Estradiol protects dopamine neurons of the substantia nigra from toxic insults. Such neurons succumb in Parkinson's disease; one strategy for restoring dopamine deficiency is cell therapy with neurons differentiated from embryonic stem cells. We investigated the effects of 17beta-estradiol on dopaminergic induction of embryonic stem cells using the...
Article
Full-text available
Neural stem cells (NSC) self-renew and generate specialized cell types. There are reports indicating that Notch and Leukemia Inhibitory Factor (LIF) signaling are involved in cell determination of NSC, either preventing differentiation or promoting astrocytic fate. In this work, we aimed to compare the astrocytogenic effect of activated Notch with...
Article
Chondroitin sulphate proteoglycans (CSPG) are components of the extracellular matrix, consisting of peptides chemically attached covalently to chains of glycosaminoglycans. There are 4 families of CSPG including lecticans, which are found mainly in the central nervous system (CNS) of vertebrates. In vitro studies have shown a negative effect of the...
Article
Class 3 Semaphorins are a subfamily of chemotropic molecules implicated in the projection of dopaminergic neurons from the ventral mesencephalon and in the formation of the nigrostriatal pathway (NSP) during embryonic development. In humans, loss of mesencephalic dopaminergic neurons leads to Parkinson's disease (PD). Cell replacement therapy with...
Article
Gamma-amino butyrate (GABA) is the most prevalent inhibitory neurotransmitter in the adult brain. In this review, we summarize the pharmacology and regulation of GABAergic transmission components (biosynthetic enzymes, receptors and transporters) in adult non-neurogenic brain regions. The effects of targeted mutations in genes relevant for GABAergi...
Article
Histamine has neurotransmitter/neuromodulator functions in the adult brain, but its role during CNS development has been elusive. We studied histamine effects on proliferation, cell death and differentiation of neuroepithelial stem cells from rat cerebral cortex in vitro. RT-PCR and Western blot experiments showed that proliferating and differentia...
Article
Embryonic stem cells (ESC) can differentiate to derivatives of the three embryonic germ layers. Dopamine neurons have been produced from mouse and human ESC. This in vitro induction mimics the developmental program followed by dopaminergic cells in vivo. Production of dopamine neurons might have clinical applications for Parkinson's disease, which...
Article
Full-text available
The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers...
Article
Because fibroblast growth factor 2 is a mitogen for central nervous system stem cells, we explored whether long-term fibroblast growth factor 2 delivery to the brain can improve functional outcome and induce cortical neurogenesis after ischemia. Rats underwent permanent distal middle cerebral artery occlusion resulting in an ischemic injury limited...
Article
The presence of glia and glial glutamate transporters seems to modify glutamate-mediated toxicity in neuronal cultures. In this work we cultured cortical cells in serum-containing medium and in a serum-free medium (Neurobasal medium + B27 supplement) and studied the expression of the glutamate transporters GLAST, GLT, and EAAC by immunocytochemistr...
Article
Full-text available
Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, e...
Article
The glutamate uptake inhibitor L-trans-2,4-pyrrolidine-dicarboxylate (PDC) induces glutamate accumulation and neuronal damage in cultured cells. We have used dissociated cortical cells in culture to study whether the toxicity induced by inhibiting glutamate uptake with PDC could be blocked by the simultaneous inhibition of gamma-aminobutyric acid (...
Article
Full-text available
Although the source of embryonic stem (ES) cells presents ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million peopl...
Article
Ruthenium red (RR) is a polycationic dye that induces neuronal death in vivo and in primary cultures. To characterize this neurotoxic action and to determine the mechanisms involved, we have analyzed the ultrastructural alterations induced by RR in rat cortical neuronal cultures and measured its effect on cytoplasmic Ca(2+) concentration ([Ca(2+)](...
Article
The hexacationic dye ruthenium red produce neuronal death in primary cultures. We injected messenger RNA (mRNA) from cultured neurons into Xenopus laevis oocytes to test whether this treatment can make oocytes sensitive to the damaging action of ruthenium red. Two-microelectrode voltage clamp and resting membrane potential were used to evaluate mRN...
Article
Phosphorylation of the inactivation gate of a K+ channel (Kv3.4) by protein kinase C (PKC) slows rapid N-type inactivation. To demonstrate that such an effect could occur under more physiological conditions, Kv3.4 and a metabotropic serotonin (5-HT) receptor were coexpressed in Xenopus oocytes. Application of 5-HT 10 microM to these oocytes produce...
Article
Ruthenium red (RR) is an inorganic polycationic dye able to exert several effects on the nervous system, including neurodegeneration, both in vivo and in cell cultures. Gangliosides have been shown to protect cultured neurons against several damaging conditions, and it has been postulated that RR can interact with the negative charges of the sialic...
Article
The inorganic polycationic dye ruthenium red (RuR) exerts several effects on the nervous system when added in physiological solutions, both in vivo and in vitro. Part of these effects, including the paralysis observed in mammals after the systemic administration of RuR, can be accounted for by the binding of RuR to nerve ending membranes, which res...
Article
It is known that neurons exposed to high concentrations of glutamate degenerate and die. The clearance of this amino acid from the extracellular space depends on their active transport by Na(+)-dependent high-affinity carriers. In the present study we tested whether inhibition of glutamate transport in mixed glial/neuronal cortical cultures induces...
Article
The inorganic dye ruthenium red (RuR) has been shown to be neurotoxic in vivo when injected intracerebrally. In this work toxicity of RuR was compared in primary cultures of rat cotical neurons, cerebellar granule neurons and cerebellar astroglia. Microscopic examination of the cultures revealed that RuR penetrates the somata of both types of neuro...

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Projects (2)
Project
To promote directed axonal growth towards chemotropic factors released from hollow nanoparticles
Archived project
We are interested in understanding whether Glial cell-Derived Neurotrophic Factor (GDNF) participates in axonal guidance in Motor Neuron and how modulates the development of Neuromuscular junction. Besides, previous studies of our own group have proven early effects of GDNF on undifferentiated ESC and we aim to clarify more precisely what is the role of GDNF in early stages of differentiation