Lei Liu

University of Massachusetts Medical School, Worcester, MA, United States

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Publications (4)41.1 Total impact

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    ABSTRACT: Human embryonic stem cells and induced pluripotent stem cells offer great hope for studies of pathogenic mechanisms of disease and cell-based therapies. One powerful approach to manipulate the behaviors of human stem cells and their progenies is through microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level. Each miRNA may target up to hundreds of mRNAs; some are specifically expressed in progenitor cells and affect multiple cellular processes. Here we present experimental protocols for investigating the endogenous functions of specific miRNAs in the proliferation, survival, and migration of human neural progenitor cells derived from embryonic stem cells. These methods may be applicable to protein factors and neural progenitor cells derived from patient-specific induced pluripotent stem cells.
    Methods in molecular biology (Clifton, N.J.) 01/2012; 916:387-402. · 1.29 Impact Factor
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    ABSTRACT: Endosomal sorting complex required for transport (ESCRT) is involved in several fundamental cellular processes and human diseases. Many mammalian ESCRT proteins have multiple isoforms but their precise functions remain largely unknown, especially in human neurons. In this study, we differentiated human embryonic stem cells (hESCs) into postmitotic neurons and characterized the functional properties of these neurons. Moreover, we found that among the three human paralogs of the yeast ESCRT-III subunit Snf7, hSnf7-1 and hSnf7-2 are most abundantly expressed in human neurons. Both hSnf7-1 and hSnf7-2 are required for the survival of human neurons, indicating a non-redundant essential function. Indeed, hSnf7-1 and hSnf7-2 are preferentially associated with CHMP2A and CHMP2B, respectively, and regulate the turnover of distinct transmembrane cargos such as neurotransmitter receptors in human neurons. These findings indicate that different mammalian paralogs of the yeast ESCRT-III subunit Snf7 have non-redundant functions in human neurons, suggesting that ESCRT-III with distinct subunit compositions may preferentially regulate different cargo proteins.
    Molecular Brain 01/2011; 4:37. · 4.20 Impact Factor
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    ABSTRACT: Human pluripotent stem cells offer promise for use in cell-based therapies for brain injury and diseases. However, their cellular behavior is poorly understood. Here we show that the expression of the brain-specific microRNA-9 (miR-9) is turned on in human neural progenitor cells (hNPCs) derived from human embryonic stem cells. Loss of miR-9 suppressed proliferation but promoted migration of hNPCs cultured in vitro. hNPCs without miR-9 activity also showed enhanced migration when transplanted into mouse embryonic brains or adult brains of a mouse model of stroke. These effects were not due to precocious differentiation of hNPCs. One of the key targets directly regulated by miR-9 encodes stathmin, which increases microtubule instability and whose expression in hNPCs correlates inversely with that of miR-9. Partial inhibition of stathmin activity suppressed the effects of miR-9 loss on proliferation and migration of human or embryonic rat neural progenitors. These results identify miR-9 as a novel regulator that coordinates the proliferation and migration of hNPCs.
    Cell stem cell 04/2010; 6(4):323-35. · 23.56 Impact Factor
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    ABSTRACT: The endosomal sorting complex required for transport (ESCRT) machinery is involved in multiple cellular processes, including autophagy (macroautophagy). Autophagy is an important intracellular pathway that involves the formation and maturation of autophagosomes and their fusion with lysosomes for bulk degradation of cytoplasmic contents and organelles. In flies and cultured mammalian cells, autophagosomes accumulate when ESCRT-III is rendered dysfunctional by reduced activity of its subunits or by ectopic expression of mutant CHMP2B associated with frontotemporal dementia linked to chromosome 3 (FTD3). Compromised ESCRT-III function results in eventual neuronal cell loss; however, the mechanism of this form of neurodegeneration is largely unknown. Recently, we found that inhibiting autophagy induction in cultured cortical neurons, either by small-molecule inhibitors of phosphatidylinositol 3-kinases (PtdIns3K) or by loss of atg5 or atg7 activity, delays but does not completely suppress neuronal cell loss caused by dysfunctional ESCRT-III. These findings indicate that excess accumulation of autophagosomes is detrimental to neuronal survival, and dysfunctional ESCRT-III appears to cause neurodegeneration through multiple mechanisms.
    Autophagy 11/2009; 5(7):1070-2. · 12.04 Impact Factor

Publication Stats

126 Citations
41.10 Total Impact Points

Institutions

  • 2012
    • University of Massachusetts Medical School
      • Department of Neurology
      Worcester, MA, United States
  • 2011
    • Hannam University
      South Korea
  • 2010
    • University of California, San Francisco
      San Francisco, California, United States
  • 2009
    • CSU Mentor
      • Department of Neurology
      Long Beach, California, United States