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Combining single-cell tracking and omics improves blood stem cell fate regulator identification.

Published version
Peer-reviewed

Type

Article

Change log

Abstract

Molecular programs initiating cell fate divergence (CFD) are difficult to identify. Current approaches usually compare cells long after CFD initiation, therefore missing molecular changes at its start. Ideally, single cells that differ in their CFD molecular program but are otherwise identical are compared early in CFD. This is possible in diverging sister cells, which were identical until their mother's division and thus differ mainly in CFD properties. In asymmetrically dividing cells, divergent daughter fates are prospectively committed during division, and diverging sisters can thus be identified at the start of CFD. Using asymmetrically dividing blood stem cells, we developed a pipeline (ie, trackSeq) for imaging, tracking, isolating, and transcriptome sequencing of single cells. Their identities, kinship, and histories are maintained throughout, massively improving molecular noise filtering and candidate identification. In addition to many identified blood stem CFD regulators, we offer here this pipeline for use in CFDs other than asymmetric division.

Description

Keywords

Cell Differentiation, Cell Division, Cell Tracking, Stem Cells

Journal Title

Blood

Conference Name

Journal ISSN

0006-4971
1528-0020

Volume Title

Publisher

American Society of Hematology
Sponsorship
Medical Research Council (MC_PC_17230)