Highlights d A single-cell bone marrow stromal cell atlas at steady-state and emergent leukemia d A portal for comparative cell and molecular analyses of bone marrow stromal cells d Distinction among putative niche cells and types of osteolineage differentiation d Leukemia remodeling of stroma to the disadvantage of normal hematopoietic cells

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~140,000 liver and ~74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the impact of tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, NK and ILC precursors in the yolk sac. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for harnessing the therapeutic potential of HSC/MPPs.

Highlights d Optimal transport analysis recovers trajectories from 315,000 scRNA-seq profiles d Induced pluripotent stem cell reprogramming produces diverse developmental programs d Regulatory analysis identifies a series of TFs predictive of specific cell fates d Transcription factor Obox6 and cytokine GDF9 increase reprogramming efficiency

We measured the viscosity of poly(ethylene glycol) (PEG 6000, 12,000, 20,000) in water using capillary electrophoresis and fluorescence correlation spectroscopy with nanoscopic probes of different diameters (from 1.7 to 114 nm). For a probe of diameter smaller than the radius of gyration of PEG (e.g. rhodamine B or lyzozyme) the measured nanoviscosity was orders of magnitude smaller than the macroviscosity. For sizes equal to (or larger than) the polymer radius of gyration, macroscopic value of viscosity was measured. A mathematical relation for macro and nanoviscosity was found as a function of PEG radius of gyration, R(g), correlation length in semi-dilute solution, xi, and probe size, R. For R < R(g), the nanoviscosity (normalized by water viscosity) is given by exp(b(R/xi)a), and for R > R(g), both nano and macroviscosity follow the same curve, exp(b(R/xi)a), where a and b are two constants close to unity. This mathematical relation was shown to equally well describe rhodamine (of size 1.7 nm) in PEG 20,000 and the macroviscosity of PEG 8,000,000, whose radius of gyration exceeds 200 nm. Additionally, for the smallest probes (rhodamine B and lysozyme) we have verified, using capillary electrophoresis and fluorescence correlation spectroscopy, that the Stokes-Einstein (SE) relation holds, providing that we use a size-dependent viscosity in the formula. The SE relation is correct even in PEG solutions of very high viscosity (three orders of magnitude larger than that of water).

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