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The spatiotemporal heterogeneity of neurons, circuits and regulators is being uncovered at a single-cell level, from single-cell gene expression to functional regulations. The classifications, architectonics and functional communications amongst neural cells and circuits within the brain can be clearly delineated using single-cell multiomics and transomics. This Editorial highlights the spatiotemporal heterogeneity of neurons and circuits as well as regulators, initiates the translation of neuronal diversity and spatial organisation at single-cell levels into clinical considerations, and enables the discovery and development of new therapies for neurological diseases. It is predicted that single-cell and spatial multiomics will be integrated with metabolomic profiles and corresponding gene epigenetic modifications. The interactions amongst DNAs, RNAs and proteins in a cell provide details of intracellular functional regulations and new opportunities for the translation of temporospatial diversity of neural cell subtypes/states into clinical practice. The application of single-cell multiomics with four-dimensional genome to the human pathological brain will lead us to a new milestone of the diagnosis and treatment., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Peripheral immune cells play important roles in the maintenance of systemic and microenvironmental hemostasis. Measurements of circulating blood cells by single-cell RNA sequencing (scRNA-seq) were proposed as one of the routine measures in clinical biochemistry of hematology. Out of translational challenges, defining precise identities of cell subsets and states is more difficult, due to the complexity of immune cell development, location, regulation, function, and metabolism. It is also a challenge to precisely interpret clinical significance and impact of each cell identity marker gene panel (ciMGPs). ciMGPs have potential to advance the understanding of systemic responses of the disease, identify disease-specific biomarkers, and to define cell heterogeneity. Recently, a large number of peripheral cell subsets and expending/activating states have been identified and validated for use in the fast developments in clinical single cell biomedicine. Defining specificity, measurability, and repeatability of cell subsets/states is important for translation of peripheral scRNA-seq in clinical hematology and biochemistry. The development of standard operating procedure and performance of clinical trials in large populations at various ages, diseases, and therapies will promote the clinical translation of ciMGPs to measures. Thus, defining cell subset/state identities will provide the multi-dimensional and comprehensive readouts of systemic immune cells, the precision monitoring of immune dynamics, and deeper-understanding of the disease and response to therapy., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

With rapid developments of single-cell sequencing and multi/trans-omics, clinical single-cell biomedicine is a new and emergent discipline to integrate single-cell molecular and clinical phenomes and uncover new disease-specific diagnoses and therapy. The journal of Clinical and Translational Medicine (CTM) launches the first CTM initiative of clinical single-cell biomedicine (cscBioMed) to promote the discovery and development of single-cell-based biology and medicine, speed the translation from single-cell biology into clinical application, and improve early diagnosis and therapy for human diseases. The cscBioMed initiative is speeding translational processes from circulating single-cell RNA sequencing into routine measures in clinical biochemistry of haematology, from spatial transcriptomics into single-cell pathology, and from single-cell-based biomarkers and targets into clinical diagnostics and target drugs. With a clear goal, we expect that cscBioMed will benefit human health by establishing a clinical single-cell dynamic monitoring and early predicting system and by improving diagnosis and treatment., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Single-cell RNA sequencing (scRNA-seq) is considered an important approach to understand the molecular mechanisms of cancer microenvironmental functions and has the potential for clinical and translational discovery and development. The recent concerns on the impact of scRNA-seq for clinical practice are whether scRNA can be applied as a routine measurement of clinical biochemistry to assist in clinical decision-making for diagnosis and therapy. Pushing single-cell sequencing into clinical application is one of the important missions for clinical and translational medicine (CTM), although there still are a large number of challenges to be overcome. The present Editorial as one of serials aims at overviewing the history of scRNA-seq publications in CTM, sharing the understanding and consideration of the cancer microenvironment at the single-cell solution and emphasising the objective of translating scRNA-seq into clinical application. The dynamic characteristics and patterns of single-cell identity, regulatory networks, and intercellular communication play decisive roles in the properties of the microenvironment, malignancy and migrative capacity of cancer cells, and defensive capacity of immune cells. The microenvironmental single-cell transcriptomic profiles and cell clusters defined by scRNA-seq have great value for exploring the molecular mechanisms of diseases and predicting cell sensitivities to therapy and patient prognosis., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)