title: MicroRNA programs in normal and aberrant stem and progenitor cells.
abstract: Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ∼22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we identified a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML1-ETO9a expression, and MLL-AF10 transformation, on self-renewal and proliferation potentials of mutant stem/progenitor cells. We showed that some of the SPT-miRNAs control the self-renewal of embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we demonstrated that SPT-miRNAs coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses reveal the miRNA programs that may control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells.
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors: Christopher P
authors: CP
authors: Arnold
authors: Ruoying
authors: R
authors: Tan
authors: Baiyu
authors: B
authors: Zhou
authors: Si-Biao
authors: SB
authors: Yue
authors: Steven
authors: S
authors: Schaffert
authors: Joseph R
authors: JR
authors: Biggs
authors: Regis
authors: R
authors: Doyonnas
authors: Miao-Chia
authors: MC
authors: Lo
authors: John M
authors: JM
authors: Perry
authors: Valérie M
authors: VM
authors: Renault
authors: Alessandra
authors: A
authors: Sacco
authors: Tim
authors: T
authors: Somervaille
authors: Patrick
authors: P
authors: Viatour
authors: Anne
authors: A
authors: Brunet
authors: Michael L
authors: ML
authors: Cleary
authors: Linheng
authors: L
authors: Li
authors: Julien
authors: J
authors: Sage
authors: Dong-Er
authors: DE
authors: Zhang
authors: Helen M
authors: HM
authors: Blau
authors: Caifu
authors: C
authors: Chen
authors: Chang-Zheng
authors: CZ
authors: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells; D009928:Organ Specificity; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D035683:MicroRNAs