The GOD of Hematopoietic Stem Cells: a Clonal Diversity Model of the Stem Cell Compartment

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2006 Feb 16

PMID 16479167

Citations 13

Authors

C E Muller-Sieburg

H B Sieburg

Affiliations

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Abstract

Hematopoietic stem cells (HSC) show heterogeneous behavior even when isolated as phenotypically homogeneous populations. The cellular and molecular mechanisms that control the generation of diversity (GOD) in the HSC compartment are not well understood, but have been the focus of much debate. There is increasing evidence that the most important HSC functions, self-renewal and differentiation, are epigenetically preprogrammed and therefore predictable. Indeed, recent data show that the adult HSC compartment consists of a limited number of functionally distinct subsets of HSC. This contradicts older models of HSC behavior, which postulated a single type of HSC that can be continuously molded into different subtypes of HSC. We propose a clonal diversity model where the adult HSC compartment consists of a fixed number of different types of HSC, each with epigenetically preprogrammed behavior. Aging or disease may change the overall function of the HSC population. The model predicts that these changes reflect the relative composition of the HSC subsets, rather than changes in individual HSC. This view has implications for using HSC in experimental and clinical settings. Selection for the appropriate subsets of HSC, rather than attempts to force HSC to adjust, should improve their utility in transplantation and gene transfer applications.

Citing Articles

New insights into hematopoietic differentiation landscapes from single-cell RNA sequencing.

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Functional Integrity and Gene Expression Profiles of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro.

Dircio-Maldonado R, Flores-Guzman P, Corral-Navarro J, Mondragon-Garcia I, Hidalgo-Miranda A, Beltran-Anaya F Stem Cells Transl Med. 2018; 7(8):602-614.

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The regulation of hematopoietic stem cell populations.

Mayani H F1000Res. 2016; 5.

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Hematopoietic stem cells: concepts, definitions, and the new reality.

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Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

Sieburg H, Cattarossi G, Muller-Sieburg C PLoS Comput Biol. 2013; 9(4):e1003006.

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