Alexander Rosenberg

To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.

This book provides a comprehensive guide to the conceptual methodological, and epistemological problems of biology, and treats in depth the major developments in molecular biology and evolutionary theory that have transformed both biology and its philosophy in recent decades. At the same time the work is a sustained argument for a particular philosophy of biology that unifies disparate issues and offers a framework for expectations about the future directions of the life sciences. The argument explores differences between autonomist and anti-autonomist views of biology. The result is a vindication of reductionism, but one that is unexpectedly hollow. For it leaves the exponents of the autonomy of biology from physical science with as much as their view of biology really requires - and rather more than the reductionist might comfortably concede. Professor Rosenberg shows how the problems of the philosophy of biology are interconnected and how their solutions are interdependent, However, this book focuses more on the direct concerns of biologists, rather than the traditional agenda of philosophers' problems about biology. This departure from earlier books on the subject results both in greater understanding and relevance of the philosophy of science to biology as a whole.

Bacterial cell gene expression Single-cell genomics in bacteria has lagged relative to in eukaryotes because of their tough bacterial cell walls, low messenger RNA content, and lack of many posttranscriptional modifications. To tackle this challenge, Kuchina et al. developed microbial split-pool ligation transcriptomics, or microSPLiT, a single-cell sequencing method for both Gram-negative and Gram-positive bacteria. Sequencing both Escherichia coli and Bacillus subtilis showed differences in the heat shock response. Examining B. subtilis transcriptional patterns revealed that a small fraction of cells grown in laboratory medium express a myo-inositol catabolism pathway, which the cell could use in nonlaboratory environments, thus highlighting how microSPLiT can identify rare cellular states. Science , this issue p. eaba5257

What makes one explanation better than another? How can we tell when an explanation has really answered our question? In a lively and readable discussion, Garfinkel argues that the key to understanding an explanation is to discover what question is really being answered. He then suggests criteria for a good explanation and goes on to examine some classic explanations in social and natural science.