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en: [Investigation of 3D chromatin structures].

en: Recent studies have revealed that multiple layers of higher-order chromatin architecture are intricately organized within the cell nucleus. While these structures are essential for the proper differentiation and function of hematopoietic cells, their dysregulation has been implicated in pathological conditions, including leukemia. Chromatin conformation capture (3C)-based methods, such as Hi-C, have revolutionized our understanding of chromatin organization and its function. Various innovative approaches have been developed to address the inherent limitations of 3C technologies. Among these, imaging-based techniques derived from fluorescence in situ hybridization, utilizing multiplexed DNA probe sets, have garnered particular attention for enabling multimodal analysis at the single-cell level. Furthermore, live-cell imaging of chromatin interactions using CRISPR-Cas9 technology is being actively developed as a powerful and practical tool. In this review, we outline the mechanisms and biological relevance of major 3D chromatin structures and highlight recent technological advances in chromatin architecture analysis.

en: [Rinsho ketsueki] The Japanese journal of clinical hematology


en: [Progress in single-cell analysis of hematopoiesis].

en: The mechanism underlying production of various types of blood cells from hematopoietic stem and progenitor cells has been a central theme in hematology. Conventionally, hematopoietic cell populations are analyzed by cell surface markers to judge cell types and differentiation stages, and by transplantation assays to assess differentiation potential. Recently, however, next-generation sequencing technology has enabled single-cell transcriptome and epigenome analyses and cell barcoding-based lineage tracing during unperturbed hematopoiesis. These innovative assays revealed that each cell population is extensively heterogenous. Many cells within hematopoietic stem cell populations may not be multipotent, and conversely, hematopoietic progenitor cells often display self-renewal capacity. Moreover, cells tend to make their lineage choice much earlier than previously thought. Altogether, these results challenge the current hierarchical differentiation models and propose new continuous models. Single-cell analyses are expected to greatly contribute to our understanding of normal and abnormal hematopoiesis and to the development of new therapies for blood disorders.

ja: [Rinsho ketsueki] The Japanese journal of clinical hematology


en: [Transcription factors in the development of myeloid cells].

en: Hematopoietic stem cells give rise to various blood cell types with diverse functions, although these different cell types harbor essentially identical genome sequences. The basis for this cell type diversity is the establishment of specific gene expression patterns through transcription factor regulation. Transcription factors recognize and bind to specific nucleotide sequences in target genes and recruit chromatin modifiers to alter the epigenetic status of these genes, thereby controlling their expression. Dysregulation of these processes can cause diseases such as leukemia. Due to rapid advances in high-throughput experimental techniques including chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA-seq, the study of transcription factors is now entering a new era. In this review, we update the current knowledge of developmental pathways in myeloid cells, particularly mononuclear phagocytes (i.e., monocytes/macrophages and dendritic cells), and the transcription factors known to be required for their development. We subsequently provide an overview of the cooperative and antagonistic mechanisms by which the myeloid transcription factors regulate their target genes, with an emphasis on chromatin biology.