Developmental regulation of myeloerythroid progenitor function by the LIN28B-LET-7-HMGA2 axis

Rowe, Grant; Wang, Leo; Coma, Sílvia; Han, A-Reum; Sousa, Patricia; Wagers, Amy J.; Daley, George Q.

doi:10.1016/j.exphem.2016.06.068

Cited by 2 publications

(3 citation statements)

References 44 publications

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“…4). The LIN28A-LIN28B/let-7 axis is a highly evolutionarily conserved developmental regulator and has emerged as a prominent feature of the fetal to adult switch in murine hematopoiesis Rowe et al 2016). …”

Section: Resultsmentioning

confidence: 99%

“…Heterogeneity within HSC populations is well established (Muller-Sieburg et al 2012) with hematopoiesis in fetal and early life representing dynamic periods of stem cell transition and maturation (Herzenberg 2015;Dykstra and de Haan 2008;Copley and Eaves 2013). In mice, potential regulators of HSC maturation include Polycomb repressor complex 2 proteins (PRC2) (Mochizuki-Kashio et al 2011;Xie et al 2014;Oshima et al 2016), SOX17 (He et al 2011), ARID3A (Ratliff et al 2014) and let-7b miRNA Rowe et al 2016). Direct tracking of stem cell lineage and diversity has been achieved in experimental animal models by enumerating chromosomal translocations, retroviral insertions and molecular barcodes in repopulating cells during hematopoietic reconstitution (Eaves 2015).…”

Section: Introductionmentioning

confidence: 99%

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Tracing human stem cell lineage during development using DNA methylation

et al. 2018

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Abstract:Stem cell maturation is a fundamental, yet poorly understood aspect of human development. We devised a DNA methylation signature deeply reminiscent of embryonal stem cells (a fetal cell origin signature, FCO) to interrogate the evolving character of multiple human tissues. The cell fraction displaying this FCO signature was highly dependent upon developmental stage (fetal vs adult), and in leukocytes, it described a dynamic transition during the first 5 years of life. Significant individual variation in the FCO signature of leukocytes was evident at birth, in childhood, and throughout adult life. The genes characterizing the signature included transcription factors and proteins intimately involved in embryonic development. We defined and applied a DNA methylation signature common among human fetal hematopoietic progenitor cells, and have shown that this signature traces the lineage of cells and informs the study of stem cell heterogeneity in humans under homeostatic conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tracing human stem cell lineage during development using DNA methylation

et al. 2018

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“…Also, LIN28B, the negative regulator of miR -Let7, is frequently overexpressed in progressive cancers 76) , and activation of the LIN28B -Let7 -HM-GA2 axis contributes to the progression of various cancers 77) . The LIN28B -Let7 -HMGA2 axis is also an essential regulator in the development of hematopoiesis but is inactivated in adulthood 78,79) . Reactivation of this pathway in HSPC could be the cause of malignant transformation, but this requires further evidence about any relationships between LIN28B and myeloid malignancies.…”

Section: Hmga2 In Myeloid Malignanciesmentioning

confidence: 99%

Cellular carcinogenesis in preleukemic conditions:drivers and defenses

Ueda,

Ikeda

2024

FJMS

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Acute myeloid leukemia (AML) arises from preleukemic conditions. We have investigated the pathogenesis of typical preleukemia, myeloproliferative neoplasms, and clonal hematopoiesis. Hematopoietic stem cells in both preleukemic conditions harbor recurrent driver mutations ; additional mutation provokes further malignant transformation, leading to AML onset. Although genetic alterations are defined as the main cause of malignant transformation, nongenetic factors are also involved in disease progression. In this review, we focus on a nonhistone chromatin protein, high mobility group AT -hook2 (HMGA2), and a physiological p53 inhibitor, murine double minute X (MDMX). HMGA2 is mainly overexpressed by dysregulation of microRNAs or mutations in polycomb components, and provokes expansion of preleukemic clones through stem cell signature disruption. MDMX is overexpressed by altered splicing balance in myeloid malignancies. MDMX induces leukemic transformation from preleukemia via suppression of p53 and p53 -independent activation of WNT/βcatenin signaling. We also discuss how these nongenetic factors can be targeted for leukemia prevention therapy.

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Developmental regulation of myeloerythroid progenitor function by the LIN28B-LET-7-HMGA2 axis

Cited by 2 publications

References 44 publications

Tracing human stem cell lineage during development using DNA methylation

Tracing human stem cell lineage during development using DNA methylation

Cellular carcinogenesis in preleukemic conditions:drivers and defenses

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