Hematopoietic stem cells sustain the continuous generation of mature blood cells throughout life. HSCs have the capacity to differentiate into any hematopoietic lineage (termed multipotency), while generating copies of themselves to preserve a relatively constant size of the HSC pool. Notably, ample evidence demonstrates that the preservation of these key properties of HSCs and their maintenance is tightly regulated by the native tissue microenvironment of bone marrow (BM) in which they reside. Albeit some of the cellular components and molecular cues participating in the control of HSC function in their anatomical niche have been described to date, a major unanswered question is how individual HSCs coordinate proliferation and differentiation to collectively maintain the homeostatic numbers in the BM. The fundamental goal of this project is to uncover the potential mechanisms underlying this collective behavior. For this we have mapped the distribution of HSCs throughout postnatal development, into adulthood and ageing and analyzed the presence of regions in which HSCs accumulate at highest densities. Our underlying hypothesis is that direct or indirect exchange of signals within such regions provide information of the state of the population and synchronize their behaviors towards the collective maintenance of the HSC population. Understanding how somatic stem cells are regulated and participate in organ homeostasis and repair is fundamental to harness the therapeutic potential of these crucial cellular subsets.Hematopoietic stem cells sustain the continuous generation of mature blood cells throughout life. HSCs have the capacity to differentiate into any hematopoietic lineage (termed multipotency), while generating copies of themselves to preserve a relatively constant size of the HSC pool (self-renewal). Notably, ample evidence demonstrates that the preservation of these key properties of HSCs and their maintenance is tightly regulated by the native tissue microenvironment of bone marrow (BM) in which they reside. Albeit multiple cellular components and molecular cues participating in the control of HSC function in their anatomical niches have been described to date, a major unanswered question is how individual HSCs coordinate proliferation and differentiation to collectively maintain the homeostatic numbers in the BM. The fundamental goal of this project is to uncover the potential mechanisms underlying this collective behavior. For this we have mapped the distribution of HSCs throughout postnatal development, into adulthood and ageing and analyzed the presence of regions in which HSCs accumulate at highest densities. Our underlying hypothesis is that direct or indirect exchange of signals within such zones provides information of the state of the population to individual HSCs and synchronizes their behavior towards the collective maintenance of the HSC population. Understanding how somatic stem cells are regulated and participate in organ homeostasis and repair is fundamental to harness the therapeutic potential of these crucial cellular subsets.
