#IDIBELLfellows: Maria Magallon / Eleni Nikolopoulou

Investigating genetic and mechanistic contributions of monosomy 7 in GATA2 deficiency
Maria Magallon Mosella – Hematopoietic Stem Cell Biology & Leukemogenesis group
GATA2 deficiency is a monogenic disorder caused by heterozygous GATA2 germline mutations. Patients present bone marrow failure, immunodeficiency, and a high risk of developing myelodysplastic neoplasms and acute myeloid leukemia (AML). Among GATA2 germline mutations, p.R396Q and p.R398W are the most commonly associated with GATA2-related MDS. Disease progression is often linked to cytogenetic alterations, such as monosomy 7, and secondary somatic mutations. In this project we attempt to identify chr7 genes cooperating with GATA2 haploinsufficiency to promote malignant transformation, utilizing a CRISPRi library targeting chr7 genes in K562 cell lines engineered to harbor GATA2 mutations (via CRISPR/Cas9) and express doxycycline-inducible catalytically inactive Cas9 fused to transcriptional repressor KRAB (idCas9-KRAB). This approach will ultimately be applied to human hematopoietic stem and progenitor cells (HSPCs).

Vascular endothelial stem cells in the regeneration of the bone marrow vascular niche
Eleni Nikolopoulou – Stem Cell Aging group
Bone marrow (BM) vascular endothelial cells serve a critical role in regulating and supporting the function and regenerative capacity of hematopoietic stem and progenitor cells. Moreover, the BM vascular network has been shown to couple angiogenesis and osteogenesis. Despite its importance in several physiological and pathophysiological conditions, the understanding of the underlying mechanisms of vascular regeneration in the BM is extremely limited. Recently, a population of tissue-resident vascular endothelial stem cells (VESCs) was identified in the liver. VESCs were characterized by the expression of CD157/BST1. Here, we investigate the stem cell potential of CD157+ BM endothelial cells by performing functional assays to measure their self-renewal and differentiation capacity. We hypothesize that an endothelial cell population with stem cell properties is present within the BM vasculature and significantly contributes to its regeneration after injury and upon aging.