Unknown,Transcriptomics,Genomics,Proteomics

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Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells


ABSTRACT: Osteolineage cells represent one of the critical bone marrow niche components that support maintenance of hematopoietic stem and progenitor cells (HSPCs). Recent studies demonstrate that extracellular vesicles (EVs) regulate stem cell development via horizontal transfer of bioactive cargo, including microRNAs (miRNAs). Here, we characterize the miRNA profile of EVs secreted by human osteoblasts and study their biological effect of on human umbilical cord blood-derived CD34+ HSPCs by sequencing, gene expression and biochemical analyses. Using next-generation sequencing we show that osteoblast-derived EVs contain highly abundant miRNAs specifically enriched in EVs, including critical regulators of hematopoietic proliferation (e.g., miR-29a). EV treatment of CD34+ HSPCs alters the expression of candidate miRNA targets, such as HBP1, BCL2 and PTEN. Furthermore, EVs enhance proliferation of CD34+ cells and their immature subsets in growth factor-driven ex vivo expansion cultures. Importantly, EV-expanded cells retain their differentiation capacity in vitro and show successful engraftment in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice in vivo. These discoveries reveal a novel osteoblast-derived EV-mediated mechanism for regulation of HSPC proliferation and warrant consideration of EV-miRNAs for the development of expansion strategies to treat hematological disorders.

INSTRUMENT(S): Illumina HiSeq 1000

ORGANISM(S): Homo sapiens

SUBMITTER: Jess Morhayim 

PROVIDER: E-MTAB-4560 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Extracellular vesicles: specialized bone messengers.

Morhayim Jess J   Baroncelli Marta M   van Leeuwen Johannes P JP  

Archives of biochemistry and biophysics 20140522


Mammalian cells actively secrete factors that contribute to shape their microenvironment. These factors either travel freely or they are enclosed within the lipid bilayer of extracellular vesicles (EVs), and regulate the function of neighboring and distant cells. EVs are secreted by a wide spectrum of cell types and are found in various biological fluids. They convey their message by mediating the horizontal transfer of bioactive molecules, such as proteins, mRNAs and miRNAs, between cells. Rece  ...[more]

Publication: 1/2

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