Yuta Izumi

Hematopoietic stem cells (HSCs) play a pivotal role in the lifelong maintenance of hematopoiesis. However, heterogeneity and age-related alterations in HSC populations hinders accurate HSC analysis. Here, we show that bone marrow (BM) macrophage fragments that preferentially express F4/80 adhere to proliferative rather than dormant HSCs. The adhesion of macrophage fragments to proliferative HSCs occurred throughout the process of BM cell preparation in vitro. Consistently, proliferative HSCs express genes involved in the adhesion of macrophage fragments at higher levels than dormant HSCs. Notably, by using that as a benchmark, dormant HSCs can be easily identified as F4/80lowHSCs throughout their lifespan, thereby revealing that they retain considerable stemness and remain functional with aging. Collectively, we propose a novel and straightforward method for the rapid identification, isolation, and analysis of distinct HSC subpopulations, which will be helpful for a wide range of hematological studies and will provide insights into HSC biology.

Conventional dendritic cells (cDCs) regulate adaptive immunity. Although most cDCs are of myeloid origin (M-cDCs), some cDCs originate from pro–plasmacytoid DCs (pro-pDCs) via pDC-like cells [lymphoid cDCs (L-cDCs)]. Using lymphoid progenitor–tracking systems, we report tissue segregation, a unique differentiation pathway, and the functions of L-cDCs. Notably, L-cDC2s are predominantly distributed in barrier tissues such as the lungs and skin. Single-cell RNA-sequencing analysis revealed the enrichment of lymphocyte signature genes in L-cDCs. We identified lymphocyte-primed cDC precursors, which are distinct from pDC-like cells, as sources of L-cDCs. Compared with M-cDC2s, L-cDC2s weakly primed T cells under low-dose antigen stimulation and preferentially promoted T helper 2 (T _H 2) differentiation under sufficient antigenic stimulation. These results suggest the diverse developmental pathways of L-cDCs and imply the contribution of L-cDCs to tolerance and hyperresponses to T _H 2-related antigens in barrier tissues.

Emergency myelopoiesis (EM) is a hematopoietic response against systemic infections that quickly supplies innate immune cells. As lymphopoiesis is strongly suppressed during EM, the role of lymphocytes in that process has not received much attention. Here, we found that myeloid-like B cells (M-B cells), which express myeloid markers, emerge in the bone marrow (BM) after the induction of EM. M-B cells were mainly derived from pre-B cells and preferentially expressed IL-10, which directly stimulates hematopoietic progenitors to enhance their survival and myeloid-biased differentiation. Indeed, lacking IL-10 in B cells, blocking IL-10 in the BM with a neutralizing antibody, and deleting the IL-10 receptor in hematopoietic progenitors significantly suppressed EM, which failed to clear microbes in a cecal ligation and puncture model. Thus, a distinct B cell subset generated during infection plays a pivotal role in boosting EM, which suggests the on-demand reinforcement of EM by adaptive immune cells.