Formación inicial de pedagogo infantil o educador preescolar. Un análisis de los perfiles ocupacional y profesional// Initial training preschool teacher or educator child. An analysis of occupational and professional profiles.

Con los procesos de registro calificado que desarrolló el programa de Licenciatura de Pedagogía Infantil de la Corporación Universitaria Rafael Núñez, se inició el proceso de comparar el programa que se pretendía certificar con otros programas afines a nivel nacional. En el mismo proceso surge la idea de realizar una investigación que diera cuenta de los procesos formativos del Pedagogo Infantil atendiendo diferente criterios, entre los que resaltamos los perfiles ocupacional, y profesional, los planes de estudio, los objetivos de los programas; formaciones en campos específicos como el de la enseñanza y aprendizaje de las matemáticas, el lenguaje, los procesos de inclusión, y otros de acuerdo a los intereses y voluntades del equipo de investigación. En este artículo se presentan los resultados al realizar un análisis de los perfiles ocupacional y profesional de los Pedagogos Infantiles o educadores preescolares publicados por las universidades en sus páginas Web. Se realiza la caracterización de la formación inicial propuesta por las universidades. La investigación se realiza siguiendo los criterios de la investigación cualitativa y se ajusta a la metodología del análisis de contenido que es la apropiada dado que nuestros objetos de estudio son los perfiles profesional y ocupacional. Inicialmente se presenta lo que entendemos por formación docente, se hace una descripción de lo que es el nivel preescolar en el sistema educativo colombiano, lo que es la formación de la maestra de preescolar, luego se hace el análisis y la interpretación de la información de los perfiles estudiados para terminar con la caracterización del la formación inicial del pedagogo infantil. Es de aclarar que los perfiles estudiados son los publicados por las Universidades en sus páginas Web. Abstract. With qualified registration processes that developed the Bachelor of Education program of the University Corporation Child Rafael Nunez, began the process of comparing the program that is intended to certify with other related programs nationwide. In the same process the idea of conducting an investigation that could account for the Child Educator training processes of different response criteria, among which we highlight the occupational profiles, and professional curricula, program objectives, training in fields specific as the teaching and learning of mathematics, language, inclusion processes, and others according to the interests and wishes of the research team

Formación inicial de pedagogo infantil o educador preescolar. Un análisis de los perfiles ocupacional y profesional// Initial training preschool teacher or educator child. An analysis of occupational and professional profiles.

Con los procesos de registro calificado que desarrolló el programa de Licenciatura de Pedagogía Infantil de la Corporación Universitaria Rafael Núñez, se inició el proceso de comparar el programa que se pretendía certificar con otros programas afines a nivel nacional. En el mismo proceso surge la idea de realizar una investigación que diera cuenta de los procesos formativos del Pedagogo Infantil atendiendo diferente criterios, entre los que resaltamos los perfiles ocupacional, y profesional, los planes de estudio, los objetivos de los programas; formaciones en campos específicos como el de la enseñanza y aprendizaje de las matemáticas, el lenguaje, los procesos de inclusión, y otros de acuerdo a los intereses y voluntades del equipo de investigación.En este artículo se presentan los resultados al realizar un análisis de los perfiles ocupacional y profesional de los Pedagogos Infantiles o educadores preescolares publicados por las universidades en sus páginas Web. Se realiza la caracterización de la formación inicial propuesta por las universidades. La investigación se realiza siguiendo los criterios de la investigación cualitativa y se ajusta a la metodología del análisis de contenido que es la apropiada dado que nuestros objetos de estudio son los perfiles profesional y ocupacional. Inicialmente se presenta lo que entendemos por formación docente, se hace una descripción de lo que es el nivel preescolar en el sistema educativo colombiano, lo que es la formación de la maestra de preescolar, luego se hace el análisis y la interpretación de la información de los perfiles estudiados para terminar con la caracterización del la formación inicial del pedagogo infantil. Es de aclarar que los perfiles estudiados son los publicados por las Universidades en sus páginas Web.Abstract.With qualified registration processes that developed the Bachelor of Education program of the University Corporation Child Rafael Nunez, began the process of comparing the program that is intended to certify with other related programs nationwide. In the same process the idea of conducting an investigation that could account for the Child Educator training processes of different response criteria, among which we highlight the occupational profiles, and professional curricula, program objectives, training in fields specific as the teaching and learning of mathematics, language, inclusion processes, and others according to the interests and wishes of the research team

C/EBP alpha and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor

Acute erythroid leukemia (AEL) commonly involves both myeloid and erythroid lineage transformation. However, the mutations that cause AEL and the cell(s) that sustain the bilineage leukemia phenotype remain unknown. We here show that combined biallelic Cebpa and Gata2 zinc finger-1 (ZnF1) mutations cooperatively induce bilineage AEL, and that the major leukemia-initiating cell (LIC) population has a neutrophil-monocyte progenitor (NMP) phenotype. In pre-leukemic NMPs Cebpa and Gata2 mutations synergize by increasing erythroid transcription factor (TF) expression and erythroid TF chromatin access, respectively, thereby installing ectopic erythroid potential. This erythroid-permissive chromatin conformation is retained in bilineage LICs. These results demonstrate that synergistic transcriptional and epigenetic reprogramming by leukemia-initiating mutations can generate neomorphic pre-leukemic progenitors, defining the lineage identity of the resulting leukemia

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation

Somatic mutations in acute myeloid leukemia are acquired sequentially and hierarchically. First, pre-leukemic mutations, such as t(8;21) that encodes AML1-ETO, are acquired within the hematopoietic stem cell (HSC) compartment, while signaling pathway mutations, including KRAS activating mutations, are late events acquired during transformation of leukemic progenitor cells and are rarely detectable in HSC. This raises the possibility that signaling pathway mutations are detrimental to clonal expansion of pre-leukemic HSC. To address this hypothesis, we used conditional genetics to introduce Aml1-ETO and K-RasG12D into murine HSC, either individually or in combination. In the absence of activated Ras, Aml1-ETO-expressing HSC conferred a competitive advantage. However, activated K-Ras had a marked detrimental effect on Aml1-ETO-expressing HSC, leading to loss of both phenotypic and functional HSC. Cell cycle analysis revealed a loss of quiescence in HSC co-expressing Aml1-ETO and K-RasG12D, accompanied by an enrichment in E2F and Myc target gene expression and depletion of HSC self-renewal-associated gene expression. These findings provide a mechanistic basis for the observed absence of KRAS signaling mutations in the pre-malignant HSC compartment

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Myelofibrosis is a severe myeloproliferative neoplasm characterized by increased numbers of abnormal bone marrow megakaryocytes that induce fibrosis, destroying the hematopoietic microenvironment. To determine the cellular and molecular basis for aberrant megakaryopoiesis in myelofibrosis, we performed single-cell transcriptome profiling of 135,929 CD34+ lineage− hematopoietic stem and progenitor cells (HSPCs), single-cell proteomics, genomics, and functional assays. We identified a bias toward megakaryocyte differentiation apparent from early multipotent stem cells in myelofibrosis and associated aberrant molecular signatures. A sub-fraction of myelofibrosis megakaryocyte progenitors (MkPs) are transcriptionally similar to healthy-donor MkPs, but the majority are disease specific, with distinct populations expressing fibrosis- and proliferation-associated genes. Mutant-clone HSPCs have increased expression of megakaryocyte-associated genes compared to wild-type HSPCs, and we provide early validation of G6B as a potential immunotherapy target. Our study paves the way for selective targeting of the myelofibrosis clone and illustrates the power of single-cell multi-omics to discover tumor-specific therapeutic targets and mediators of tissue fibrosis

Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a poor-prognosis childhood leukemia usually caused by RAS-pathway mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population. Single-cell HSPC index-sorting and clonogenic assays show that (1) all somatic mutations can be backtracked to the phenotypic HSC compartment, with RAS-pathway mutations as a "first hit,"(2) mutations are acquired with both linear and branching patterns of clonal evolution, and (3) mutant HSPCs are present after allogeneic HSC transplant before molecular/clinical evidence of relapse. Stem cell assays reveal interpatient heterogeneity of JMML LSCs, which are present in, but not confined to, the phenotypic HSC compartment. RNA sequencing of JMML LSC reveals upregulation of stem cell and fetal genes (HLF, MEIS1, CNN3, VNN2, and HMGA2) and candidate therapeutic targets/biomarkers (MTOR, SLC2A1, and CD96), paving the way for LSC-directed disease monitoring and therapy in this disease

Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner

Hematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. However, feedback mechanisms by which HSCs, through their niches, sense acute losses of specific blood cell lineages remain to be established. While all HSCs replenish platelets, previous studies have shown that a large fraction of HSCs are molecularly primed for the megakaryocyte-platelet lineage and are rapidly recruited into proliferation upon platelet depletion. Platelets normally turnover in an activation-dependent manner, herein mimicked by antibodies inducing platelet activation and depletion. Antibody-mediated platelet activation upregulates expression of Interleukin-1 (IL-1) in platelets, and in bone marrow extracellular fluid in vivo. Genetic experiments demonstrate that rather than IL-1 directly activating HSCs, activation of bone marrow Lepr+ perivascular niche cells expressing IL-1 receptor is critical for the optimal activation of quiescent HSCs upon platelet activation and depletion. These findings identify a feedback mechanism by which activation-induced depletion of a mature blood cell lineage leads to a niche-dependent activation of HSCs to reinstate its homeostasis