“A Role for the Bone Marrow Niche in Regulating the Hematopoietic Stem Cell Response to Stress Hematopoiesis”, Tiago C. Luis, Imperial College London, United Kingdom

Speaker: Dr. Tiago C. Luis, Imperial College London, United Kingdom

Host: Postdoc Network DKFZ

Abstract

Hematopoietic stem cells (HSC) are responsible for the on demand production of mature blood cells both in homeostasis and in response to stress situations such as injury and infection. HSCs reside in specialized niches in bone marrow (BM), which beyond physical support are essential to regulate their function.

These niches are perceived as dynamic entities with the capacity to sense and respond to specific requirements in blood production, but the mechanisms underlying this dynamic regulation remain unclear. Accumulating evidence indicate that HSCs are highly heterogeneous, and different BM niches have been proposed, potentially supporting different subsets of HSCs.

The Luis Lab recently identified a distinct subset of HSCs, which are molecularly and functionally primed for platelet replenishment. In response to platelet depletion platelet-biased HSCs are rapidly and selectively recruited into cell cycle, through a feedback mechanism to replenish platelet numbers and homeostasis. However, the role of the niche in the regulation of platelet-biased HSC function is still unknown.

Therefore, they investigated the role of the BM niche in the response of platelet-biased HSCs to thrombocytopenia and, used RNA-sequencing to analyze different BM niche cell populations to identify signals involved in the HSC response to platelet depletion. Here they identified Interleukin-1 (IL-1) as a cytokine released upon acute platelet depletion and specifically sensed by niche perivascular cells.

Abrogation of IL-1 signaling specifically in LepR+ niche cells but not in hematopoietic cells impaired the platelet-biased HSC response to platelet depletion. This work uncovers a molecular mechanism involving the pro-inflammatory signal IL-1 and the niche perivascular cell compartment in the rapid activation of platelet biased HSCs to thrombocytopenia, highlighting a mechanism by which a distinct subclass of HSCs senses and responds to the loss of the lineage for which it is intrinsically primed for.

About Tiago

Tiago Luis research focuses on the hematopoietic system and more specifically on the mechanisms regulating hematopoietic stem and progenitor cells (HSC) function and the extracellular signals these cells receive from their niches.

During his PhD at Erasmus Medical Centre (Rotterdam, The Netherlands) he studied the role of the Wnt signaling pathway in hematopoiesis and demonstrated a stage/lineage-specific and dosage-dependent effect of canonical Wnt signaling throughout hematopoiesis. After his PhD, Tiago joined the laboratory of Prof. Sten Eirik Jacobsen at the University of Oxford (UK) as an EMBO postdoctoral fellow, to investigate the cellular pathways of lineage commitment from HSCs. He characterized the first hematopoietic progenitors that migrate and colonize the fetal thymus, where they encounter a specific microenvironment eliciting further differentiation through the T-lymphocyte lineage.

In 2014 he as awarded a Kay Kendall Leukaemia Fund Fellowship to investigate the bone marrow niche of platelet-biased HSCs. In 2018 he was awarded a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society to start his laboratory at Imperial College London to investigate the molecular mechanisms by which the BM niche regulates HSCs, in stress hematopoiesis and in the development of hematological malignancies.