DOI: 10.1101/503813Dec 21, 2018Paper

Cell division history determines hematopoietic stem cell potency

BioRxiv : the Preprint Server for Biology
Fumio AraiBen MacArthur

Abstract

Changes in the ability of individual stem cells to self-renew based on their developmental history may underpin aging. Here, we developed a high-throughput paired daughter cell assay that combines single cell profiling with machine learning and mathematical modeling to probe in detail how multivariate gene expression patterns change through hematopoietic stem cell (HSC) divisions. We first collated a library of single cell gene expression patterns from various different cell types in the hematopoietic hierarchy taken from young, adult and aged mice. We then trained an artificial neural network (ANN) to accurately predict both cellular identity and developmental age directly from gene expression profiles. Once this classifier had been trained we used it to investigate HSC division patterns. To do so, we isolated highly purified long term repopulating HSCs, allowed them to divide in various different culture conditions, separated daughter cells using a micro-manipulator, immediately profiled their gene expression patterns, and used our trained ANN to compare daughter cells identities. We found that the propensity of individual HSCs to divide symmetrically or asymmetrically changed dramatically with age, with self-renewal ability ...Continue Reading

Related Concepts

Aging
Cell Division
Gene Expression
Hematopoiesis
Hematopoietic Stem Cells
Intrinsic factor
Learning
Lymphocyte
Laboratory mice
Stem Cells

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