Rudolf Jaenisch
Massachusetts Institute of Technology
Publications 608
Microglia are essential for maintenance of normal brain function, with dysregulation contributing to numerous neurological diseases. Protocols have been developed to derive microglia-like cells from human induced pluripotent stem cells (hiPSCs). However, primary microglia display major differences in morphology and gene expression when grown in culture, including down-regulation of signature microglial genes. Thus, in vitro differentiated microglia may not accurately represent resting primary mi...
Genetic studies of epigenetic modifiers such as DNA methyltransferases and histone acetyltransferases have revealed a critical role for epigenetic regulation during brain development and function. Alteration of epigenetic modifications have been documented in a variety of brain disorders, including neurodevelopmental, psychiatric, and neurodegenerative diseases. Development of epigenome editing tools enables a functional dissection of the link between altered epigenetic changes and disease outco...
#1Karen E. Ocwieja (Boston Children's Hospital)H-Index: 1
#2Alexandra Stanton (Harvard University)
Last.Lee Gehrke (MIT: Massachusetts Institute of Technology)H-Index: 31
view all 8 authors...
#1Yuelin Song (MIT: Massachusetts Institute of Technology)H-Index: 1
#2Patrick R. van den Berg (LEI: Leiden University)H-Index: 4
Last.Rudolf Jaenisch (MIT: Massachusetts Institute of Technology)H-Index: 175
view all 13 authors...
Summary Variable levels of DNA methylation have been reported at tissue-specific differential methylation regions (DMRs) overlapping enhancers, including super-enhancers (SEs) associated with key cell identity genes, but the mechanisms responsible for this intriguing behavior are not well understood. We used allele-specific reporters at the endogenous Sox2 and Mir290 SEs in embryonic stem cells and found that the allelic DNA methylation state is dynamically switching, resulting in cell-to-cell h...
1 CitationsSource
#1Xin Tang (MIT: Massachusetts Institute of Technology)H-Index: 7
#2Jesse Drotar (MIT: Massachusetts Institute of Technology)H-Index: 2
Last.Rudolf Jaenisch (MIT: Massachusetts Institute of Technology)H-Index: 175
view all 12 authors...
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl CpG binding protein 2 (MECP2) gene. There are currently no approved treatments for RTT. The expression of K+/Cl− cotransporter 2 (KCC2), a neuron-specific protein, has been found to be reduced in human RTT neurons and in RTT mouse models, suggesting that KCC2 might play a role in the pathophysiology of RTT. To develop neuron-based high-throughput screening (HTS) assays to identify chemical compounds that enhan...
4 CitationsSource
#1Tian V. TianH-Index: 2
#2Bruno Di Stefano (Harvard University)H-Index: 15
Last.Tanja Graf (UPF: Pompeu Fabra University)H-Index: 75
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How pluripotent stem cells differentiate into the main germ layers is a key question of developmental biology. Here, we show that the chromatin-related factor Whsc1 (also known as Nsd2 and MMSET) has a dual role in pluripotency exit and germ layer specification of embryonic stem cells. On induction of differentiation, a proportion of Whsc1-depleted embryonic stem cells remain entrapped in a pluripotent state and fail to form mesendoderm, although they are still capable of generating neuroectoder...
1 CitationsSource
#1Julien Pontis (EPFL: École Polytechnique Fédérale de Lausanne)H-Index: 2
#2Evarist Planet (EPFL: École Polytechnique Fédérale de Lausanne)H-Index: 12
Last.Didier Trono (EPFL: École Polytechnique Fédérale de Lausanne)H-Index: 85
view all 9 authors...
Summary Expansion of transposable elements (TEs) coincides with evolutionary shifts in gene expression. TEs frequently harbor binding sites for transcriptional regulators, thus enabling coordinated genome-wide activation of species- and context-specific gene expression programs, but such regulation must be balanced against their genotoxic potential. Here, we show that Kruppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) control the timely and pleiotropic activation of TE-derived...
11 CitationsSource
#1Yun Li (MIT: Massachusetts Institute of Technology)H-Index: 12
#2Julien Muffat (MIT: Massachusetts Institute of Technology)H-Index: 17
Last.Rudolf Jaenisch (MIT: Massachusetts Institute of Technology)H-Index: 175
view all 11 authors...
Zika virus (ZIKV) is a neurotropic and neurovirulent arbovirus that has severe detrimental impact on the developing human fetal brain. To date, little is known about the factors required for ZIKV infection of human neural cells. We identified ZIKV host genes in human pluripotent stem cell (hPSC)-derived neural progenitors (NPs) using a genome-wide CRISPR-Cas9 knockout screen. Mutations of host factors involved in heparan sulfation, endocytosis, endoplasmic reticulum processing, Golgi function, a...
1 CitationsSource
#1John D. GraefH-Index: 5
#2Hao WuH-Index: 82
view all 11 authors...
Fragile X Syndrome (FXS) is the most common genetic form of intellectual disability caused by a CGG repeat expansion in the 5′-UTR of the Fragile X mental retardation gene FMR1, triggering epigenetic silencing and the subsequent absence of the protein, FMRP. Reactivation of FMR1 represents an attractive therapeutic strategy targeting the genetic root cause of FXS. However, largely missing in the FXS field is an understanding of how much FMR1 reactivation is required to rescue FMRP-dependent muta...
#1Saranna Fanning (MIT: Massachusetts Institute of Technology)H-Index: 12
#2Aftabul Haque (MIT: Massachusetts Institute of Technology)H-Index: 1
Last.Dennis J. Selkoe (Brigham and Women's Hospital)H-Index: 162
view all 31 authors...
Summary In Parkinson’s disease (PD), α-synuclein (αS) pathologically impacts the brain, a highly lipid-rich organ. We investigated how alterations in αS or lipid/fatty acid homeostasis affect each other. Lipidomic profiling of human αS-expressing yeast revealed increases in oleic acid (OA, 18:1), diglycerides, and triglycerides. These findings were recapitulated in rodent and human neuronal models of αS dyshomeostasis (overexpression; patient-derived triplication or E46K mutation; E46K mice). Pr...
14 CitationsSource