Visualization of individual cell division history in complex tissues

The division potential of individual stem cells and the molecular consequences of successive rounds of proliferation remain largely unknown. We developed an inducible cell division counter (iCOUNT) that reports cell division events in human and mouse tissues in vitro and in vivo. Analysing cell division histories of neural stem/progenitor cells (NSPCs) in the developing and adult brain, we show that iCOUNT allows for novel insights into stem cell behaviour. Further, we used single cell RNA-sequencing (scRNA-seq) of iCOUNT-labelled NSPCs and their progenies from the developing mouse cortex and forebrain-regionalized human organoids to identify molecular pathways that are commonly regulated between mouse and human cells, depending on individual cell division histories. Thus, we developed a novel tool to characterize the molecular consequences of repeated cell divisions of stem cells that allows an analysis of the cellular principles underlying tissue formation, homeostasis, and repair. HighlightsO_LIiCOUNT reports previous cell divisions in mouse and human cells in vitro C_LIO_LIiCOUNT detects cell division biographies in complex mouse tissues in vivo C_LIO_LIiCOUNT allows for the analysis of human neural stem/progenitor cells in human forebrain organoids C_LIO_LISingle cell RNA-sequencing of iCOUNT cells derived from the mouse developing cortex and human forebrain organoids identifies molecular consequences of previous rounds of cell divisions C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/266171v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@144b085org.highwire.dtl.DTLVardef@a10b2forg.highwire.dtl.DTLVardef@e57053org.highwire.dtl.DTLVardef@1316c11_HPS_FORMAT_FIGEXP M_FIG C_FIG