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Slaughter, A.

Publications and source records attributed to Slaughter, A..

3 recordsLinked to original sources

Resilient anatomy and local microplasticity of na&iumlve and stress hematopoiesis

The bone marrow has an extraordinary capacity to adjust blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses is largely unknown due to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent hematopoiesis, megakaryopoiesis, erythropoiesis, and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of hematopoiesis in homeostasis, after acute insults, and during geriatric age. Blood production takes place via long-range migration of multipotent progenitors away from stem cells. Lineage-committed progenitors are then serially recruited to blood vessels where they contribute to lineage-specific microanatomical structures, composed of progenitors and immature cells, which function as production lines for mature blood cells. This anatomy is durable and resilient to insults as it was maintained after hemorrhage, acute bacterial infection, and with aging. Production lines enable hematopoietic plasticity as they differentially -and selectively-modulate their numbers and output in response to acute insults and then return to homeostasis. In geriatric mice the number of production lines is maintained, but their microanatomy becomes permanently remodeled in a cell- and lineage-specific manner indicating chronic anatomical adaptations to hematopoietic aging. Our studies uncover the sophisticated and durable anatomy of blood production -defined by distinct migratory behaviors depending on the maturation stage- and identify discrete microanatomical production lines that confer plasticity to hematopoiesis.

physiology↗

Feeding habits and novel prey of larval fishes in the northern San Francisco Estuary

Food limitation can dampen survival and growth of fish during early development. To investigate prey diversity important to the planktivorous larval longfin smelt (Spirinchus thaleichthys) and Pacific herring (Clupea pallasii) from the San Francisco Estuary, we used DNA metabarcoding analysis of the cytochrome oxidase I gene on the guts of these fishes and on environmental zooplankton samples. Differential abundance analysis suggested that both species consumed the most abundant zooplankton at a lower rate than their availability in the environment. Both fish consumed the prey that were commonly available and relatively abundant. Prey taxa substantially overlapped between the two species (Schoeners index = 0.66), and alpha diversity analysis suggested high variability in the content of individual guts. Abundant prey taxa in both fish species included the copepods Eurytemora carolleeae, Acanthocyclops americanus, and A. robustus; the Acanthocyclops spp. are difficult to identify morphologically. A few uncommon prey in the diets hint at variable feeding strategies, such as herring (presumably egg) DNA in the longfin smelt diets, which suggests feeding near substrates. Herring consumed the small (<0.5 mm) copepod Limnoithona tetraspina more frequently (30%) than did smelt (2%), possibly indicating differences in foraging behavior or sensory abilities. Among the unexpected prey found in the diets was the cnidarian Hydra oligactis, the polychaete Dasybranchus sp., and a newly identified species Mesocyclops pehpeiensis. "Unknown" DNA was in 56% of longfin smelt diets and 57% of herring diets, and made up 17% and 21% of the relative read abundance in the two species, respectively. Our results suggest that these two fishes, which overlap in nursery habitat, also largely overlap in food resources necessary for larval survival.

ecology↗

Three-dimensional mapping identifies distinct vascular niches for myelopoiesis

In contrast to virtually all other tissues in the body the anatomy of differentiation in the bone marrow remains unknown. This is due to the lack of strategies to examine blood cell production in situ, which are required to better understand differentiation, lineage commitment decisions, and to define how spatial organizing cues inform tissue function. Here we developed imaging approaches to map all myeloid cells in whole bones and generated 3D atlases of granulocyte and monocyte/dendritic cell differentiation during homeostasis. We found that myeloid progenitors leave the hematopoietic stem cell niche during differentiation. Granulocyte and monocyte dendritic cell progenitors (MDP) do not interact, instead they localize to different sinusoids where they give rise to clusters of immature cells. MDP cluster with Ly6Clo monocytes and conventional dendritic cells; these localize to a unique subset of colony stimulating factor 1 (CSF1, the major regulator of monopoiesis1) -expressing sinusoids. Csf1 deletion in the vasculature disrupted the MDP clusters and their interaction with sinusoids, leading to reduced MDP numbers and differentiation ability, with subsequent loss of peripheral Ly6Clo monocytes and dendritic cells. These data indicate that there is a specific spatial organization of definitive hematopoiesis and that local cues produced by distinct blood vessels are responsible for this organization. These maps provide a blueprint for in situ analyses of hematopoiesis in blood disorders.

immunology↗