Stem cell regulatory niches and their role in normal and malignant hematopoiesis.
OBJECTIVE
In the postnatal life, hematopoietic stem cell (HSC) niches are specialized microenvironments in the bone marrow that are essential for the maintenance and function of HSCs. The purpose of this review is to discuss the concept of HSC niche in light of recent studies that broaden its complexity and better define its molecular regulation. Also, we will discuss recent studies addressing the impact of leukemia development on HSC regulation and normal hematopoiesis, while discussing the potential regulation of leukemia-initiating cells by bone marrow niches.


RESULTS
Recent studies have identified new cellular and molecular components of the HSC niche and highlighted reciprocal interactions between the hematopoietic cells and their niches. These studies indicate that the HSC niche is not constituted by a single cell type but rather should be considered as a multicellular functional unit. Finally, advances have been made that provide promising insights into the the instructive role of the bone marrow microenvironment in hematological malignancies.


CONCLUSIONS
Increasing insights into the cell-cell cross talk between the hematopoietic system and its microenvironment in the bone marrow, and in particular in the interplay of HSCs with their niche(s), should provide new tools for combinatorial therapies in bone marrow failure and bone marrow cancers.
Carlesso
Nadia
N
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ncarless@iupui.edu
Cardoso
Angelo A
AA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D055153:Stem Cell Niche / Q000166:cytology / Q000378:metabolism / Q000502:physiology*