Model human clonal hematopoiesis : using the CRISPR/Cas9 system

Hematopoietic malignancies are genetically complex diseases in which the serial acquisition of somatic mutations results in clonal diversity of hematopoietic stem and progenitor cells (HSPCs). This progressive event where clonal expansion and selection involved in clonal dynamics of HSPCs is called...

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Autor principal: Lo, Yi-Hsuan
Otros Autores: Roth, Berta
Formato: Tesis de maestría acceptedVersion
Lenguaje:Inglés
Publicado: Facultad de Farmacia y Bioquímica 2019
Materias:
Clonal hematopoiesis
CRISPR/Cas9
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5943
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5943.dir/5943.PDF
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-HWA_5943
record_format dspace
spelling I28-R145-HWA_59432022-04-12 Hematopoietic malignancies are genetically complex diseases in which the serial acquisition of somatic mutations results in clonal diversity of hematopoietic stem and progenitor cells (HSPCs). This progressive event where clonal expansion and selection involved in clonal dynamics of HSPCs is called clonal hematopoiesis of indeterminate potential (CHIP). CHIP increases with age and can be found in 10% of the elderly. CHIP is associated with an increased risk to develop myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). In this study, we used CRISPR/Cas9 genome engineering in cell lines and primary human cells to introduce somatic mutations in the driver genes STAG2 and TP53 with the final goal to generate in vitro models of clonal hematopoiesis in primary adult CD34+ human HSPCs. We will use these models to further evaluate the underlying mechanism of clonal hematopoiesis and potential transformation into hematological malignancies related to dysregulation of the cell cycle, increased genomic alterations and chromosomal instability. Fil: Lo, Yi-Hsuan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Roth, Berta Facultad de Farmacia y Bioquímica Wäsch, Ralph Lo, Yi-Hsuan 2019-03-26 Las enfermedades malignas hematopoyéticas son enfermedades genéticamente complejas en las que la adquisición en serie de mutaciones somáticas da como resultado la diversidad clonal de células madre y progenitoras hematopoyéticas (HSPCs). Este evento progresivo donde la expansión y selección clonal involucrada en la dinámica clonal de HSPCs se llama hematopoyesis clonal de potencial indeterminado (CHIP). CHIP aumenta con la edad y se puede encontrar en el 10% de los ancianos. CHIP se asocia con un mayor riesgo de desarrollar síndrome mielodisplásico (MDS) o leucemia mieloide aguda (AML). En este estudio, utilizamos la ingeniería del genoma CRISPR/Cas9 en líneas celulares y células humanas primarias para introducir mutaciones somáticas en los genes controladores STAG2 y TP53 con el objetivo final de generar modelos in vitro de hematopoyesis clonal en adultos adultos CD34+ HSPCs humanos. Utilizaremos estos modelos para evaluar más a fondo el mecanismo subyacente de la hematopoyesis clonal y la posible transformación en tumores malignos hematológicos relacionados con la desregulación del ciclo celular, el aumento de las alteraciones genómicas y la inestabilidad cromosómica. application/pdf Ranuncolo, Stella Pereyra-Bonnet, Federico Aktories, Klaus Clonal hematopoiesis CRISPR/Cas9 eng Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Model human clonal hematopoiesis : using the CRISPR/Cas9 system info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5943 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5943.dir/5943.PDF
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Inglés
orig_language_str_mv eng
topic Clonal hematopoiesis
CRISPR/Cas9
Ciencias de la vida
spellingShingle Clonal hematopoiesis
CRISPR/Cas9
Ciencias de la vida
Lo, Yi-Hsuan
Model human clonal hematopoiesis : using the CRISPR/Cas9 system
topic_facet Clonal hematopoiesis
CRISPR/Cas9
Ciencias de la vida
description Hematopoietic malignancies are genetically complex diseases in which the serial acquisition of somatic mutations results in clonal diversity of hematopoietic stem and progenitor cells (HSPCs). This progressive event where clonal expansion and selection involved in clonal dynamics of HSPCs is called clonal hematopoiesis of indeterminate potential (CHIP). CHIP increases with age and can be found in 10% of the elderly. CHIP is associated with an increased risk to develop myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). In this study, we used CRISPR/Cas9 genome engineering in cell lines and primary human cells to introduce somatic mutations in the driver genes STAG2 and TP53 with the final goal to generate in vitro models of clonal hematopoiesis in primary adult CD34+ human HSPCs. We will use these models to further evaluate the underlying mechanism of clonal hematopoiesis and potential transformation into hematological malignancies related to dysregulation of the cell cycle, increased genomic alterations and chromosomal instability.
author2 Roth, Berta
author_facet Roth, Berta
Lo, Yi-Hsuan
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Lo, Yi-Hsuan
author_sort Lo, Yi-Hsuan
title Model human clonal hematopoiesis : using the CRISPR/Cas9 system
title_short Model human clonal hematopoiesis : using the CRISPR/Cas9 system
title_full Model human clonal hematopoiesis : using the CRISPR/Cas9 system
title_fullStr Model human clonal hematopoiesis : using the CRISPR/Cas9 system
title_full_unstemmed Model human clonal hematopoiesis : using the CRISPR/Cas9 system
title_sort model human clonal hematopoiesis : using the crispr/cas9 system
publisher Facultad de Farmacia y Bioquímica
publishDate 2019
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5943
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5943.dir/5943.PDF
work_keys_str_mv AT loyihsuan modelhumanclonalhematopoiesisusingthecrisprcas9system
_version_ 1766017555699335168

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