New insights into transcriptional mechanisms that preserve hematopoietic stem cell homeostasis
- Autores: Laia Traveset Martínez
- Directores de la Tesis: José Francisco Aramburu Beltrán (dir. tes.), Cristina López Rodríguez (codir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2020
- Idioma: español
- Tribunal Calificador de la Tesis: Anna Bigas Salvans (presid.), Alberto Yáñez (secret.), Maria Carolina Florian (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Maintenance of steady-state and stress-adapted hematopoiesis depends on the fitness of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Hematopoietic stem cells (HSCs) can adapt to stress by expanding their numbers and increasing the output of blood cells. This dynamic and highly complex process needs to be fully regulated in order to maintain a balance between the differentiation of HSCs and the need to keep a constant pool of HSCs. However, the molecular machinery in charge of this tight regulation has yet to be fully characterized. HSCs represent a small proportion inside the HSPC compartment, which also includes the immediate progeny of HSCs, the multipotent progenitors (MPP). MPPs are a cell population that retain full lineage potential yet have a limited self-renewal capacity compared to HSC.
In this Thesis we explore a novel mechanism important for the maintenance and protection of HSC function under stress. We have characterized HSC homeostasis and function upon serial transplantation, after myeloablative injury and after a protocol of total body irradiation. We present in vivo results elucidating a new transcription mechanism involved in the maintenance of the viability and self-renewal capacity of HSCs that restrains its differentiation to MPPs, in situations in which the hematopoietic system must keep constant the stem cell reservoir in order to avoid HSC exhaustion.
