SLS Special Seminar | Chen Weng: Deciphering cell states and genealogies of human hematopoiesis with single-cell multi-omics

Time:4:00-5:30 PM,Monday, Dec. 5th,2022

Host:Dr. Shutao Qi, Research Professor, School of Life Sciences

Venue:E9-109, Yungu Compus


Dr. Chen Weng, Postdoctoral fellow, Whitehead Institute and Broad Institute of Harvard and MIT

Chen Weng studies genomics and epigenomics in stem cell differentiation and development. He develops and applies cutting-edge single-cell omics and lineage tracing technologies to study cell fate navigations in health and disease. He completed his Ph.D at Case Western Reserve University and joined Jonathan Weissman Lab and Vijay Sankaran Lab at Whitehead Institute and Broad Institute of Harvard and MIT in 2021.


The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived hematopoietic stem cells (HSCs). Perturbations to this process underlie a diverse set of diseases, but the clonal contributions to human hematopoiesis and how this changes with age remain incompletely understood. While recent insights have emerged from barcoding studies in model systems, simultaneous detection of cell states and phylogenies from natural barcodes in humans has been challenging, which has limited the ability to explore functional differences between HSC clones. Here, we introduce an improved single-cell lineage tracing system based on deep detection of naturally-occurring mitochondrial DNA (mtDNA) mutations with simultaneous readout of transcriptional states and chromatin accessibility. We use this system to define the clonal architecture of HSCs, and map the physiological state and output of these clones. We uncover functional heterogeneity in HSC clones, which is stable over months and manifests as differences in total HSC output as well as biases toward the production of different mature blood and immune lineages. We also find that the diversity of HSC clones decreases dramatically with age leading to an oligoclonal structure with multiple distinct clonal expansions. Our study thus provides the first clonally-resolved and cell-state aware atlas of human hematopoiesis at single-cell resolution revealing an unappreciated functional diversity of human HSC clones both in young and aged individuals and more broadly paves the way for refined studies of clonal dynamics across a range of tissues in human health and disease.


Wenyue Yu:

School of Life Sciences