Lin28b Reprograms Adult Bone Marrow Hematopoietic Progenitors to Mediate Fetal-Like Lymphopoiesis

Yuan, Joan; Nguyen, Cuong K.; Liu, Xiuhuai; Kanellopoulou, Chrysi; Muljo, Stefan A.

doi:10.1126/science.1216557

Cited by 297 publications

(409 citation statements)

References 60 publications

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“…Recently, two studies have suggested that Lin28a/b reexpression can counteract the developmental decline in cell regeneration and tissue repair. In both cases, let-7 repression was necessary to mediate this effect, although let-7 repression alone was not sufficient to enhance tissue repair (58,59). To determine whether LIN28B reexpression might enhance SC plasticity, LIN28B was reexpressed in the late embryonic (E15.5) cochlea and the ability of SCs to generate new HCs in response to γ-secretase inhibitor treatment was analyzed in early postnatal (P2) cochlear explant cultures (Fig.…”

Section: Lin28b Overexpression Results In a Delay In Prosensory Cell mentioning

confidence: 99%

The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea

Golden

Benito-Gonzalez

Doetzlhofer

2015

Proc. Natl. Acad. Sci. U.S.A.

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Proper tissue development requires strict coordination of proliferation, growth, and differentiation. Strict coordination is particularly important for the auditory sensory epithelium, where deviations from the normal spatial and temporal pattern of auditory progenitor cell (prosensory cell) proliferation and differentiation result in abnormal cellular organization and, thus, auditory dysfunction. The molecular mechanisms involved in the timing and coordination of auditory prosensory proliferation and differentiation are poorly understood. Here we identify the RNAbinding protein LIN28B as a critical regulator of developmental timing in the murine cochlea. We show that Lin28b and its opposing let-7 miRNAs are differentially expressed in the auditory sensory lineage, with Lin28b being highly expressed in undifferentiated prosensory cells and let-7 miRNAs being highly expressed in their progeny-hair cells (HCs) and supporting cells (SCs). Using recently developed transgenic mouse models for LIN28B and let-7g, we demonstrate that prolonged LIN28B expression delays prosensory cell cycle withdrawal and differentiation, resulting in HC and SC patterning and maturation defects. Surprisingly, let-7g overexpression, although capable of inducing premature prosensory cell cycle exit, failed to induce premature HC differentiation, suggesting that LIN28B's functional role in the timing of differentiation uses let-7 independent mechanisms. Finally, we demonstrate that overexpression of LIN28B or let-7g can significantly alter the postnatal production of HCs in response to Notch inhibition; LIN28B has a positive effect on HC production, whereas let-7 antagonizes this process. Together, these results implicate a key role for the LIN28B/let-7 axis in regulating postnatal SC plasticity.Lin28b | Let-7 | hair cell | cochlea | regeneration

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Section: Lin28b Overexpression Results In a Delay In Prosensory Cell mentioning

confidence: 99%

The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea

Golden

Benito-Gonzalez

Doetzlhofer

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The mammalian genome encodes two homologues of the C. elegans lin-28 genes (LIN28A and LIN28B) (3,4), which may control gene expression by distinct molecular mechanisms (5). They are important in processes such as embryogenesis (6), skeletal myogenesis (7), germ cell development (8,9), neurogliogenesis (10,11), differentiation (12,13), lymphopoiesis (14), and glucose metabolism (15). Genome-wide association studies have implicated the LIN28B locus in controlling both height and the timing of menarche in humans (16 -20).…”

mentioning

confidence: 99%

Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer

Zhong

Lin

et al. 2012

Journal of Biological Chemistry

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Background: LIN28A may function as a critical oncogene in human cancer. Results: LIN28A controls expression of numerous cell cycle regulatory genes, including CDK2, CCND1, and CDC25A, in cancer. Conclusion: LIN28A promotes cell cycle progression in cancer mediated by both let-7-dependent and -independent mechanisms. Significance: Our data shed new light on how LIN28A regulates cell cycle in cancer.

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“…Erythropoietin-treated CD45 + fibroblasts overexpressing Oct-4 generate erythroid cells expressing adult β-globin protein rather than embryonic ζ-globin [22] [23]. Although these two studies are not comparable because of distinct species, starting cells, and transcription factors, it can be concluded that such a route of dedifferentiation may not be the only one.…”

Section: Dedifferentiationmentioning

confidence: 84%

Advances in cell lineage reprogramming

Zhou¹,

Yue²,

Pei³

2013

Sci. China Life Sci.

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As a milestone breakthrough of stem cell and regenerative medicine in recent years, somatic cell reprogramming has opened up new applications of regenerative medicine by breaking through the ethical shackles of embryonic stem cells. However, induced pluripotent stem (iPS) cells are prepared with a complicated protocol that results in a low reprogramming rate. To obtain differentiated target cells, iPS cells and embryonic stem cells still need to be induced using step-by-step procedures. The safety of induced target cells from iPS cells is currently a further concerning matter. More broadly conceived is lineage reprogramming that has been investigated since 1987. Adult stem cell plasticity, which triggered interest in stem cell research at the end of the last century, can also be included in the scope of lineage reprogramming. With the promotion of iPS cell research, lineage reprogramming is now considered as one of the most promising fields in regenerative medicine, will hopefully lead to customized, personalized therapeutic options for patients in the future.

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Lin28b Reprograms Adult Bone Marrow Hematopoietic Progenitors to Mediate Fetal-Like Lymphopoiesis

Cited by 297 publications

References 60 publications

The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea

The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea

Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer

Advances in cell lineage reprogramming

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