Kinetics of adult hematopoietic stem cell differentiation in vivo

Samik Upadhaya, Catherine M. Sawai, Efthymia Papalexi, Ali Rashidfarrokhi, Geunhyo Jang, Pratip Chattopadhyay, Rahul Satija, Boris Reizis

Research output: Contribution to journalArticlepeer-review


Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.

Original languageEnglish (US)
Pages (from-to)2815-2832
Number of pages18
JournalJournal of Experimental Medicine
Issue number11
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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