Transcriptome Dynamics of Hematopoietic Stem Cell Formation Revealed Using a Combinatorial Runx1 and Ly6a Reporter System

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2020 Apr 18

PMID 32302558

Citations 6

Authors

Michael J Chen

Edroaldo Lummertz da Rocha

Patrick Cahan

Caroline Kubaczka

Phoebe Hunter

Patricia Sousa

Nathaniel K Mullin

Yuko Fujiwara

Minh Nguyen

Yuqi Tan

Samuel Landry

Areum Han

Song Yang

Yi-Fen Lu

Deepak Kumar Jha

Linda T Vo

Yi Zhou

Trista E North

Leonard I Zon

George Q Daley

Thorsten M Schlaeger

Affiliations

Soon will be listed here.

Abstract

Studies of hematopoietic stem cell (HSC) development from pre-HSC-producing hemogenic endothelial cells (HECs) are hampered by the rarity of these cells and the presence of other cell types with overlapping marker expression profiles. We generated a Tg(Runx1-mKO2; Ly6a-GFP) dual reporter mouse to visualize hematopoietic commitment and study pre-HSC emergence and maturation. Runx1-mKO2 marked all intra-arterial HECs and hematopoietic cluster cells (HCCs), including pre-HSCs, myeloid- and lymphoid progenitors, and HSCs themselves. However, HSC and lymphoid potential were almost exclusively found in reporter double-positive (DP) cells. Robust HSC activity was first detected in DP cells of the placenta, reflecting the importance of this niche for (pre-)HSC maturation and expansion before the fetal liver stage. A time course analysis by single-cell RNA sequencing revealed that as pre-HSCs mature into fetal liver stage HSCs, they show signs of interferon exposure, exhibit signatures of multi-lineage differentiation gene expression, and develop a prolonged cell cycle reminiscent of quiescent adult HSCs.

Citing Articles

Lineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells.

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CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development.

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