Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development

• DOI: 10.1016/j.celrep.2021.109698
• Publication Date: 2021-09-14T21:36:13Z
• Authors: Anindita Roy; Guanlin Wang; Deena Iskander; Sorcha O’Byrne; Natalina Elliott; Jennifer O’Sullivan; Gemma Buck; Elisabeth F. Heuston; Wei Xiong Wen; Alba Rodriguez Meira; Peng Hua; Anastasios Karadi...; Adam J. Mead; David M. Bodine; Irene Roberts; Bethan Psaila; Supat Thongjuea
• Keywords: Resource; 0301 basic medicine; 0303 health sciences; single-cell genomics; QH301-705.5; Sequence Analysis, RNA; Cell Differentiation; Hematopoietic Stem Cells; hematopoiesis; Hematopoiesis; 3. Good health; 03 medical and health sciences; human development; single-cell RNA sequencing analysis; Humans; Cell Lineage; Gene Regulatory Networks; Biology (General); Single-Cell Analysis; Transcriptome; stem/progenitor cells; Signal Transduction

Human hematopoiesis is a dynamic process that starts in utero 18-21 days post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartment changes during human ontogeny and the underlying gene regulatory mechanisms, we compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime. Single-cell transcriptomic analysis identifies significant site- and developmental stage-specific transitions in cellular architecture and gene regulatory networks. Hematopoietic stem cells show progression from cycling to quiescence and increased inflammatory signaling during ontogeny. We demonstrate the utility of this dataset for understanding aberrant hematopoiesis through comparison to two cancers that present at distinct time points in postnatal life-juvenile myelomonocytic leukemia, a childhood cancer, and myelofibrosis, which classically presents in older adults.