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The Hematopoietic Stem Cell Niche: Cell-Cell Interactions and Quiescence

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Biology in Stem Cell Niche

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Recently much progress has been made in describing the biology of hematopoietic stem cells (HSCs) and their interaction with various components of the niche in which they reside. These components, cellular and structural, have profound implications on HSC maintenance and quiescence. This chapter systematically reviews these interactions organized by cell type, niche component, or physiological condition. Cell type interactions are examined according to lineage such as endothelium, cells of mesenchymal origin (e.g. Nestin+ cells and osteoblasts [OBs]), and others (e.g. megakaryocytes [MKs] and non-myelinating Schwann cells). Physical niche components such as the extra cellular matrix proteins are also discussed, along with the chemical milieu. Finally, intrinsic regulators of HSC function are considered. This chapter is not intended to be an exhaustive account of HSC niche biology; however, relevant mechanistic information is included. Also, where appropriate, we draw special attention to niche cells and components with effects on HSC quiescence.

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Abbreviations

6C3:

ENPEP glutamyl aminopeptidoase (aminopeptidase A)

Ang1:

Angiopoietin 1

Arf :

ADP-ribosylation factor

CAR:

CXCL 12 abundant reticular cells

CD:

Cluster of differentiation

CDI:

Cyclin dependent kinase inhibitor

CFU-F:

Colony forming unit fibroblastic

c-Kit:

Identify hematopoietic progenitors, Kit oncogene

CXCL12:

Chemokine (C-X-C motif) ligand 12

CXCR4:

C-X-C motif chemokine receptor 4

DTR:

Diphtheria toxin receptor

ECM:

Extracellular matrix

FACS:

Fluorescent-activated cell sorting

FLT3:

Fms-like tyrosine kinase 3

Fmi:

Flamingo

Fz8:

Frizzled 8

G-CSF(R):

Granulocyte colony-stimulating factor (receptor)

GFAP:

Glial fibrillary acid protein

GFP:

Green Fluorescent Protein

GRP78:

Glucose-regulated protein 78

HIF-1:

Hypoxia-inducible factor

HPC(s):

Hematopoietic progenitor cell(s)

HSC(s):

Hematopoietic stem cell(s)

HSPC(s):

Hematopoietic stem and progenitor cell(s)

ICAM:

Intercellular adhesion molecule

IL:

Interleukin

INFγ:

Interferon gamma

KitL:

Kit ligand also stem cell factor or SCF

Lep-R:

Leptin receptor (CD295)

Lin− :

Lineage negative

LSK:

Lin−Scal+ c-Kit+

LTBP:

Latent TGFB1 binding protein

LT-HSCs:

Long-term repopulating HSCs

MCAM:

Melanoma cell adhesion molecule

MK(s):

Megakaryocyte(s)

MSC(s):

Mesenchymal stem/stromal cell(s)

MSPC(s):

Mesenchymal stem/progenitor cell(s)

mTOR:

Mammalian target of rapamycin

Nestin:

Intermediate filament protein

NFAT:

Nuclear factor of activated T-cells

OM:

Osteomacs

p57Kip2:

Cyclin-dependent kinase inhibitor 1C

PDGFR:

Platelet derived growth factor receptor

PF4:

Platelet factor 4 (also CXCL4)

PIMO:

Pimonidazole, hypoxia marker

PTH:

Parathyroid hormone

RNA-seq:

Ribonucleic acid sequencing

ROS:

Reactive oxygen species

Runx2:

Runt-related transcription factor 2

Satb1:

Transcription factor/chromatin remodeling protein

Sca1:

Stem cell antigen-1

SCF:

Stem cell factor

SDF1:

CXCL12

TCA:

Tricarboxylic acid cycle

TGFB1:

Transforming growth factor beta 1

TPO:

Thrombopoietin

VCAM1:

Vascular cell adhesion molecule 1

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Acknowledgments

This work was supported in part by NIAMS AR060332 (MAK), NIA AG046246 (MAK), the Indiana Center for Excellence in Molecular Hematology (NIDDK P30 DK090948), and a postdoctoral NIH T32 Training Grant in Hematopoiesis, T32 4689736 (PC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, 1130 W. Michigan Street, FH 115, IN, 46202, USA

    Paul J. Childress, Marta B. Alvarez & Melissa A. Kacena

  2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Marta B. Alvarez & Melissa A. Kacena

  3. Indiana University School of Medicine, 980 W. Walnut Street, R3-C312, Indianapolis, IN, 46202, USA

    Brahmananda R. Chitteti & Edward F. Srour

  4. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA

    Edward F. Srour

  5. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    Edward F. Srour

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  1. Paul J. Childress
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  2. Marta B. Alvarez
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  3. Brahmananda R. Chitteti
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  4. Melissa A. Kacena
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  5. Edward F. Srour
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Corresponding authors

Correspondence to Melissa A. Kacena or Edward F. Srour .

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Editors and Affiliations

  1. Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Kursad Turksen

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Childress, P.J., Alvarez, M.B., Chitteti, B.R., Kacena, M.A., Srour, E.F. (2015). The Hematopoietic Stem Cell Niche: Cell-Cell Interactions and Quiescence. In: Turksen, K. (eds) Biology in Stem Cell Niche. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-21702-4_1

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