The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression

Mehta, Arnav; Zhao, Jimmy L.; Sinha, Nikita; Marinov, Georgi K.; Mann, Mati; Kowalczyk, Monika S.; Galimidi, Rachel P.; Du, Xiaomi; Erikçi, Erdem; Regev, Aviv; Chowdhury, Kamal; Baltimore, David

doi:10.1016/j.immuni.2015.05.017

Cited by 87 publications

(80 citation statements)

References 39 publications

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“…We have recently shown that this microRNA cluster helps maintain normal hematopoietic stem cell output with age by buffering Foxo3 protein levels (Mehta et al, 2015). The current study demonstrates that miR-212/132 maintains B cell output through a different mechanism, serving more as a gatekeeper that modulates Sox4 protein levels when increased B cell output is required.…”

Section: Microrna-132 Protects E-myc Mice From B Cell Leukemia Develmentioning

confidence: 67%

“…We have previously shown that Sox4 mRNA expression levels are decreased in the bone marrow of WT miR-132 mice compared with WT MG controls (Mehta et al, 2015). Sox4 has a conserved, computationally predicted 7mer-m8 binding site for miR-132 (Fig.…”

Section: Enforced Expression Of Microrna-132 Inhibits B Cell Developmentmentioning

confidence: 89%

“…Recently, the microRNA-212/132 cluster (miR-212/132) has emerged as an important regulator of hematopoietic stem cell function (Mehta et al, 2015), antiviral immunity (Lagos et al, 2010), macrophage and T H 17 T cell immune function (Taganov et al, 2006;Shaked et al, 2009;Nahid et al, 2013;Nakahama et al, 2013), and inflammation and proliferation during wound healing (Li et al, 2015). In addition, it has been shown that miR-132 plays a role in the proliferation and invasion of certain solid tumors (Zhang et al, 2014;Jiang et al, 2015), as well as in pathological angiogenesis (Anand et al, 2010), thus making it a potential candidate for cancer therapeutics.…”

Section: Enforced Expression Of Microrna-132 Inhibits B Cell Developmentmentioning

confidence: 99%

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The microRNA-212/132 cluster regulates B cell development by targeting Sox4

Mehta¹,

Mann²,

Zhao³

et al. 2015

J Cell Biol

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Section: Microrna-132 Protects E-myc Mice From B Cell Leukemia Develmentioning

confidence: 67%

Section: Enforced Expression Of Microrna-132 Inhibits B Cell Developmentmentioning

confidence: 89%

Section: Enforced Expression Of Microrna-132 Inhibits B Cell Developmentmentioning

confidence: 99%

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The microRNA-212/132 cluster regulates B cell development by targeting Sox4

Mehta¹,

Mann²,

Zhao³

et al. 2015

J Cell Biol

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“…Studies of vascular component in the formation of HSCs niches allowed have a new vision of the endosteal niche as it became clear that the influence of this region is not confined to the endosteal surface, as has been assumed initially [145,146]. As has already been mentioned, the BM in the endosteal region is well vascularized with arterioles and venous sinusoids with CAR-cells [105].…”

Section: Perivascular and Endothelial Cellsmentioning

confidence: 90%

“…Thus enhancement of miR-132 expression in the BM of mice stimulates the proliferation of HSCs and decreases their number. It is notable that miR-132 effect is mediated by the transcription factor FOXO3 [146].…”

Section: Intracellular Factorsmentioning

confidence: 99%

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Nikolskaya¹,

Butenko²

2016

JCOT

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This article focuses on (1) the analysis of the structural-functional organization of bone marrow niches of the hematopoietic stem cells, (2) the role of the intercellular contact interactions and humoral regulation factors in these niches, in particular CXCL12, SCF and TGFβ,and (3) KEYWORDS: bone marrow, hematopoietic stem cell niche, multipotent stromal cells, hematopoiesisMaksimov and finally established at the end of the past century, it is not only the number but also entire known diversity of cell elements of immune and blood systems originate from only one type of the progenitor elements -the HSCs (unitary theory) [2].Life force and productivity of the HSCs is proved, for example, by the fact that 99.9 % of all blood-generating cells, HSCs included, in the irradiated mice can perish, and the surviving stem cells rapidly renew blood formation, including proper population as well as all types of the committed progenitors [3]. Along same sequence, the fact of non-exhaustion of blood formation after repeated damaging exposures is explained by the presence and functioning of the HSCs [1].The specialized cells of adult and fetal periods of ontogenesis, residing in the bone marrow (BM) in the quiescent state and capable, together with blood-forming microenvironment, to realize underlying programs for self-maintenance and multipotency allowing them (with maintained amount of HSCs) to release necessary amount of cells into differentiation along various directions that ultimately leads to the formation of all forms of blood elements, including immune system cells. It should be noted that the self-maintenance is not identical to the immortality. Stem cells are characterized by sufficiently long life, commensurable with entire organism's life course. Several genetic regulatory programs have been established which are of great importance in the process of HSCs self-maintenance. It is also known that stem cells in various tissues are controlled by common genetic programs maintaining their nature [4,5].It is theorized that stem cells are the clonogenic units which under certain conditions can be increased in their number at the expense Immune system is the structural-functional and interrelated commonness of the hematopoietic and stromal cells. Different in their origin, structure and functions, the populations and subpopulations of lymphoid and myeloid cells make a complete wholeness in the definite tissues and organs where they closely cooperate with non-hematopoietic elements. Constant and strictly regulated intensity of hematopoiesis with production of various cell types is also conditioned and controlled by cooperation of the hematopoietic and stromal cells. Timely repopulation of the immune system with hematopoietic cells-precursors, lymphocytes, leucocytes and stromal cells, newly maturing in the bone marrow, is the main condition for effective immune system functioning. The number of cells formed per time unit is plentiful. According to the given data, nearly 10 11 neutrophils (about 100 g of mass) per...

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Micro‐RNAs: A safety net to protect hematopoietic stem cell self‐renewal

Crisafulli

Ficara

2021

WIREs RNA

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The hematopoietic system is sustained over time by a small pool of hematopoietic stem cells (HSCs). They reside at the apex of a complex hierarchy composed of cells with progressively more restricted lineage potential, regenerative capacity, and with different proliferation characteristics. Like other somatic stem cells, HSCs are endowed with long‐term self‐renewal and multipotent differentiation ability, to sustain the high turnover of mature cells such as erythrocytes or granulocytes, and to rapidly respond to acute peripheral stresses including bleeding, infections, or inflammation. Maintenance of both attributes over time, and of the proper balance between these opposite features, is crucial to ensure the homeostasis of the hematopoietic system. Micro‐RNAs (miRNAs) are short non‐coding RNAs that regulate gene expression posttranscriptionally upon binding to specific mRNA targets. In the past 10 years they have emerged as important players for preserving the HSC pool by acting on several biological mechanisms, such as maintenance of the quiescent state while preserving proliferation ability, prevention of apoptosis, premature differentiation, lineage skewing, excessive expansion, or retention within the BM niche. miRNA‐mediated posttranscriptional fine‐tuning of all these processes constitutes a safety mechanism to protect HSCs, by complementing the action of transcription factors and of other regulators and avoiding unwanted expansion or aplasia. The current knowledge of miRNAs function in different aspects of HSC biology, including consequences of aberrant miRNA expression, will be reviewed; yet unsolved issues will be discussed. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development

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The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression

Cited by 87 publications

References 39 publications

The microRNA-212/132 cluster regulates B cell development by targeting Sox4

The microRNA-212/132 cluster regulates B cell development by targeting Sox4

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Micro‐RNAs: A safety net to protect hematopoietic stem cell self‐renewal

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