Itzel Escobedo - Academia.edu (original) (raw)

Papers by Itzel Escobedo

Research paper thumbnail of Transcriptome Profiling after Early Spinal Cord Injury in the Axolotl and Its Comparison with Rodent Animal Models through RNA-Seq Data Analysis

Research paper thumbnail of Human Embryonic Stem Cell-Derived Immature Midbrain Dopaminergic Neurons Transplanted in Parkinsonian Monkeys

Research paper thumbnail of Establishment of induced pluripotent stem cell lines derived from Parkinson’s disease Mexican patients: A sporadic (UNAMi002-A) and a familial (UNAMi003-A) case carrying a mutation in PINK1

Stem cell research, Feb 1, 2024

Research paper thumbnail of Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage

International Journal of Molecular Sciences

Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the... more Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the blood-borne spread of specific microorganisms, provoke nervous tissue damage due to the inflammatory process. Moreover, different pathologies such as sepsis can generate systemic inflammation. Bacterial lipopolysaccharide (LPS) induces the release of inflammatory mediators and damage molecules, which are then released into the bloodstream and can interact with structures such as the CNS, thus modifying the blood–brain barrier’s (BBB´s) and blood–cerebrospinal fluid barrier´s (BCSFB´s) function and inducing aseptic neuroinflammation. During neuroinflammation, the participation of glial cells (astrocytes, microglia, and oligodendrocytes) plays an important role. They release cytokines, chemokines, reactive oxygen species, nitrogen species, peptides, and even excitatory amino acids that lead to neuronal damage. The neurons undergo morphological and functional changes that could initiate fu...

Research paper thumbnail of Generation of a human induced pluripotent stem cell line (UNAMi001-A) from a Mexican patient with sporadic Parkinson’s disease

Research paper thumbnail of Supplemental Material, sj-tif-1-cll-10.1177_0963689720978219 - Human Keratinocytes Adopt Neuronal Fates After <i>In Utero</i> Transplantation in the Developing Rat Brain

Supplemental Material, sj-tif-1-cll-10.1177_0963689720978219 for Human Keratinocytes Adopt Neuron... more Supplemental Material, sj-tif-1-cll-10.1177_0963689720978219 for Human Keratinocytes Adopt Neuronal Fates After <i>In Utero</i> Transplantation in the Developing Rat Brain by Andrea Tenorio-Mina, Daniel Cortés, Joel Esquivel-Estudillo, Adolfo López-Ornelas, Alejandro Cabrera-Wrooman, Rolando Lara-Rodarte, Itzel Escobedo-Avila, Fernanda Vargas-Romero, Diana Toledo-Hernández, Enrique Estudillo, Juan José Acevedo-Fernández, Jesús Santa-Olalla Tapia and Iván Velasco in Cell Transplantation

Research paper thumbnail of Human embryonic stem cells-derived dopaminergic neurons transplanted in parkinsonian monkeys recover dopamine levels and motor behavior

bioRxiv, 2020

Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopam... more 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’s disease (PD) patients. We obtained DAN from hESCs and confirmed that they express dopaminergic markers, generate action potentials, and release dopamine (DA) in vitro. DAN were transplanted bilaterally in the putamen of parkinsonian NHPs. After grafting, animals improved motor behavior, evaluated by the HALLWAY task, and in agreement with this recovery, DA release was detected by microdialysis. Imaging techniques revealed changes in fractional anisotropy and mean diffusivity in magnetic resonance imaging and higher 11C-DTBZ binding in positron-emission tomography scans, associated with grafts. Postmortem analysis showed that transplanted DAN survived over ten months in the putamen, without developing tumors, in the immunosuppressed N...

Research paper thumbnail of Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain

Cell Transplantation, 2021

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with... more 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 we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injec...

Research paper thumbnail of Modeling the neuromuscular junction in vitro : an approach to study neuromuscular junction disorders

Annals of the New York Academy of Sciences, 2020

The neuromuscular junction (NMJ) is a specialized structure that works as an interface to transla... more 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 also to generate conditions that recapitulate distinct features of diseases. Initial studies relied on the use of tissue slices maintained under the same environment and in which single motor axons were difficult to trace. Later, MNs and muscle cells were obtained from primary cultures or differentiation of progenitors and cocultured as monolayers; however, the tissue architecture was lost. Current approaches include self‐assembling 3D structures or the incorporation of biomaterials with cells to generate engineered tissues, although the incorporation of Schwann cells remains a challenge. Thus, numerous investigations have established different NMJ models, some of which are quite complex and challenging. Our review summarizes the in vitro models that have emerged in recent years to coculture MNs and skeletal muscle, trying to mimic the healthy and diseased NMJ. We expect our review may serve as a reference for choosing the appropriate experimental model for the required purposes of investigation.

Research paper thumbnail of Histamine Modulates Midbrain Dopamine Neuron Differentiation Through the Regulation of Epigenetic Marks

Frontiers in Cellular Neuroscience, 2019

During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic proc... more During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic processes such as DNA methylation and demethylation as well as posttranslational modification of histones occur during neurogenesis. Here, we administered histamine (HA) into the brain of E12 embryos in vivo and observed significant lower immunoreactivity of Lmx1a+ and Tyrosine Hydroxylase (TH)+ cells, with parallel decreases in the expression of early (Lmx1a, Msx1) and late (Th) midbrain dopaminergic (mDA) genes. With MeDIP assays we found that HA decreases the percentage of 5-methylcytosine of Pitx3 and Th, without changes in 5-hydroxymethylcytosine. Additionally, HA treatment caused a significant increase in the repressive epigenetic modifications H3K9me3 in Pitx3 and Th, and also more H3K27me3 marks in Th. Furthermore, HA has a long-term effect on the formation of the nigrostriatal and mesolimbic/mesocortical pathways, since it causes a significant decrease in midbrain TH immunoreactivity, as well as alterations in dopaminergic neuronal fibers, and significant lower TH-positive area in the forebrain in whole-mount stainings. These findings suggest that HA diminishes dopaminergic gene transcription by altering several epigenetic components related to DNA and histone modifications, which affects mDA neuron progression during development.

Research paper thumbnail of Transgenic GDNF Positively Influences Proliferation, Differentiation, Maturation and Survival of Motor Neurons Produced from Mouse Embryonic Stem Cells

Frontiers in Cellular Neuroscience, 2016

Research paper thumbnail of Histamine up-regulates fibroblast growth factor receptor 1 and increases FOXP2 neurons in cultured neural precursors by histamine type 1 receptor activation: conceivable role of histamine in neurogenesis during cortical development in vivo

Neural Development, 2013

Background During rat development, histamine (HA) is one of the first neuroactive molecules to ap... more 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 cerebrocortical neural precursor cultures, that micromolar HA enhanced the effect of fibroblast growth factor (FGF)-2 on proliferation, and that HA increased neuronal differentiation, due to HA type 1 receptor (H1R) activation. Results Clonal experiments performed here showed that HA decreased colony size and caused a significant increase in the percentage of clones containing mature neurons through H1R stimulation. In proliferating precursors, we studied whether HA activates G protein-coupled receptors linked to intracellular calcium increases. Neural cells presented an increase in cytoplasmic calcium even in the absence of extracellular calci...

Research paper thumbnail of Histamine impairs midbrain dopaminergic development in vivo by activating histamine type 1 receptors

Research paper thumbnail of Histamine promotes neuronal differentiation of midbrain neural stem cells

Research paper thumbnail of Transcriptome Profiling after Early Spinal Cord Injury in the Axolotl and Its Comparison with Rodent Animal Models through RNA-Seq Data Analysis

Research paper thumbnail of Human Embryonic Stem Cell-Derived Immature Midbrain Dopaminergic Neurons Transplanted in Parkinsonian Monkeys

Research paper thumbnail of Establishment of induced pluripotent stem cell lines derived from Parkinson’s disease Mexican patients: A sporadic (UNAMi002-A) and a familial (UNAMi003-A) case carrying a mutation in PINK1

Stem cell research, Feb 1, 2024

Research paper thumbnail of Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage

International Journal of Molecular Sciences

Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the... more Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the blood-borne spread of specific microorganisms, provoke nervous tissue damage due to the inflammatory process. Moreover, different pathologies such as sepsis can generate systemic inflammation. Bacterial lipopolysaccharide (LPS) induces the release of inflammatory mediators and damage molecules, which are then released into the bloodstream and can interact with structures such as the CNS, thus modifying the blood–brain barrier’s (BBB´s) and blood–cerebrospinal fluid barrier´s (BCSFB´s) function and inducing aseptic neuroinflammation. During neuroinflammation, the participation of glial cells (astrocytes, microglia, and oligodendrocytes) plays an important role. They release cytokines, chemokines, reactive oxygen species, nitrogen species, peptides, and even excitatory amino acids that lead to neuronal damage. The neurons undergo morphological and functional changes that could initiate fu...

Research paper thumbnail of Generation of a human induced pluripotent stem cell line (UNAMi001-A) from a Mexican patient with sporadic Parkinson’s disease

Research paper thumbnail of Supplemental Material, sj-tif-1-cll-10.1177_0963689720978219 - Human Keratinocytes Adopt Neuronal Fates After <i>In Utero</i> Transplantation in the Developing Rat Brain

Supplemental Material, sj-tif-1-cll-10.1177_0963689720978219 for Human Keratinocytes Adopt Neuron... more Supplemental Material, sj-tif-1-cll-10.1177_0963689720978219 for Human Keratinocytes Adopt Neuronal Fates After <i>In Utero</i> Transplantation in the Developing Rat Brain by Andrea Tenorio-Mina, Daniel Cortés, Joel Esquivel-Estudillo, Adolfo López-Ornelas, Alejandro Cabrera-Wrooman, Rolando Lara-Rodarte, Itzel Escobedo-Avila, Fernanda Vargas-Romero, Diana Toledo-Hernández, Enrique Estudillo, Juan José Acevedo-Fernández, Jesús Santa-Olalla Tapia and Iván Velasco in Cell Transplantation

Research paper thumbnail of Human embryonic stem cells-derived dopaminergic neurons transplanted in parkinsonian monkeys recover dopamine levels and motor behavior

bioRxiv, 2020

Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopam... more 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’s disease (PD) patients. We obtained DAN from hESCs and confirmed that they express dopaminergic markers, generate action potentials, and release dopamine (DA) in vitro. DAN were transplanted bilaterally in the putamen of parkinsonian NHPs. After grafting, animals improved motor behavior, evaluated by the HALLWAY task, and in agreement with this recovery, DA release was detected by microdialysis. Imaging techniques revealed changes in fractional anisotropy and mean diffusivity in magnetic resonance imaging and higher 11C-DTBZ binding in positron-emission tomography scans, associated with grafts. Postmortem analysis showed that transplanted DAN survived over ten months in the putamen, without developing tumors, in the immunosuppressed N...

Research paper thumbnail of Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain

Cell Transplantation, 2021

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with... more 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 we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injec...

Research paper thumbnail of Modeling the neuromuscular junction in vitro : an approach to study neuromuscular junction disorders

Annals of the New York Academy of Sciences, 2020

The neuromuscular junction (NMJ) is a specialized structure that works as an interface to transla... more 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 also to generate conditions that recapitulate distinct features of diseases. Initial studies relied on the use of tissue slices maintained under the same environment and in which single motor axons were difficult to trace. Later, MNs and muscle cells were obtained from primary cultures or differentiation of progenitors and cocultured as monolayers; however, the tissue architecture was lost. Current approaches include self‐assembling 3D structures or the incorporation of biomaterials with cells to generate engineered tissues, although the incorporation of Schwann cells remains a challenge. Thus, numerous investigations have established different NMJ models, some of which are quite complex and challenging. Our review summarizes the in vitro models that have emerged in recent years to coculture MNs and skeletal muscle, trying to mimic the healthy and diseased NMJ. We expect our review may serve as a reference for choosing the appropriate experimental model for the required purposes of investigation.

Research paper thumbnail of Histamine Modulates Midbrain Dopamine Neuron Differentiation Through the Regulation of Epigenetic Marks

Frontiers in Cellular Neuroscience, 2019

During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic proc... more During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic processes such as DNA methylation and demethylation as well as posttranslational modification of histones occur during neurogenesis. Here, we administered histamine (HA) into the brain of E12 embryos in vivo and observed significant lower immunoreactivity of Lmx1a+ and Tyrosine Hydroxylase (TH)+ cells, with parallel decreases in the expression of early (Lmx1a, Msx1) and late (Th) midbrain dopaminergic (mDA) genes. With MeDIP assays we found that HA decreases the percentage of 5-methylcytosine of Pitx3 and Th, without changes in 5-hydroxymethylcytosine. Additionally, HA treatment caused a significant increase in the repressive epigenetic modifications H3K9me3 in Pitx3 and Th, and also more H3K27me3 marks in Th. Furthermore, HA has a long-term effect on the formation of the nigrostriatal and mesolimbic/mesocortical pathways, since it causes a significant decrease in midbrain TH immunoreactivity, as well as alterations in dopaminergic neuronal fibers, and significant lower TH-positive area in the forebrain in whole-mount stainings. These findings suggest that HA diminishes dopaminergic gene transcription by altering several epigenetic components related to DNA and histone modifications, which affects mDA neuron progression during development.

Research paper thumbnail of Transgenic GDNF Positively Influences Proliferation, Differentiation, Maturation and Survival of Motor Neurons Produced from Mouse Embryonic Stem Cells

Frontiers in Cellular Neuroscience, 2016

Research paper thumbnail of Histamine up-regulates fibroblast growth factor receptor 1 and increases FOXP2 neurons in cultured neural precursors by histamine type 1 receptor activation: conceivable role of histamine in neurogenesis during cortical development in vivo

Neural Development, 2013

Background During rat development, histamine (HA) is one of the first neuroactive molecules to ap... more 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 cerebrocortical neural precursor cultures, that micromolar HA enhanced the effect of fibroblast growth factor (FGF)-2 on proliferation, and that HA increased neuronal differentiation, due to HA type 1 receptor (H1R) activation. Results Clonal experiments performed here showed that HA decreased colony size and caused a significant increase in the percentage of clones containing mature neurons through H1R stimulation. In proliferating precursors, we studied whether HA activates G protein-coupled receptors linked to intracellular calcium increases. Neural cells presented an increase in cytoplasmic calcium even in the absence of extracellular calci...

Research paper thumbnail of Histamine impairs midbrain dopaminergic development in vivo by activating histamine type 1 receptors

Research paper thumbnail of Histamine promotes neuronal differentiation of midbrain neural stem cells