Graphical AbstractHighlights d Myeloid scRNA-seq atlas across brain regions and developmental stages d Limited transcriptomic heterogeneity of homeostatic microglia in the adult brain d Phase-specific gene sets of proliferating microglia along cell cycle pseudotime d Phagocytic PAM subset uncovered by scRNA-seq sharing a DAM gene signature SUMMARY Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing (scRNA-seq) of microglia and related myeloid cells sorted from various regions of embryonic, early postnatal, and adult mouse brains. We found that the majority of adult microglia expressing homeostatic genes are remarkably similar in transcriptomes, regardless of brain region. By contrast, early postnatal microglia are more heterogeneous.We discovered a proliferative-region-associated microglia (PAM) subset, mainly found in developing white matter, that shares a characteristic gene signature with degenerative disease-associated microglia (DAM). Such PAM have amoeboid morphology, are metabolically active, and phagocytose newly formed oligodendrocytes. This scRNA-seq atlas will be a valuable resource for dissecting innate immune functions in health and disease.

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We combine diffuse optical and correlation spectroscopies to simultaneously measure the oxyhemoglobin and deoxyhemoglobin concentration and blood flow in an adult human brain during sensorimotor stimulation. The observations permit calculation of the relative cerebral metabolic rate of oxygen in the human brain, for the first time to our knowledge, by use of all-optical methods. The feasibility for noninvasive optical measurement of blood flow through the skull of an adult brain is thus demonstrated, and the clinical potential of this hybrid, all-optical noninvasive, methodology can now be explored.

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We have employed near-infrared optical methods to measure noninvasively the dynamics of muscle blood flow and oxygen saturation (StO2) during cuff occlusion and plantar flexion exercise. Relative muscle oxygen consumption (rVO2) was also computed from these data. Diffuse correlation spectroscopy provides information about blood flow, and diffuse reflectance spectroscopy provides information about blood oxygenation. Ten healthy subjects and one patient with peripheral arterial disease (PAD) were studied during 3-min arterial cuff occlusion of arm and leg, and during 1-min plantar flexion exercise. Signals from different layers (cutaneous tissues and muscles) during cuff occlusion were differentiated, revealing strong hemodynamic responses from muscle layers. During exercise in healthy legs, the observed approximately 4.7 fold increase in relative blood flow (rBF) was significantly lower than the corresponding increase in rVO2 (approximately 7 fold). The magnitudes of rBF and rVO2 during exercise in the PAD patient were approximately 1/2 of the healthy controls, and the StO2 recovery time was twice that of the controls. The hybrid instrument improves upon current technologies for measuring muscle responses by simultaneously measuring rBF and StO2. The instrument thus provides a method for evaluation of microcirculation and muscle metabolism in patients with vascular diseases.