Iacovitti Research

Petruk, Svetlana, Jingli Cai, Robyn Sussman, Guizhi Sun, Sina K. Kovermann, Samanta A. Mariani, Bruno Calabretta, Steven B. McMahon, Hugh W. Brock, Lorraine Iacovitti and Alexander Mazo. 2017. “Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation.” Molecular Cell 66 (2): 247.

We discovered that during the first hours of induction of differentiation of mammalian embryonic stem cells (ESCs), accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome. This delay provides a critical “window of opportunity” for recruitment of lineage-specific TFs to DNA.

Lin, Ruihe, Jingli Cai, Cody Nathan, Xiaotao Wei, Stephanie Schleidt, Robert Rosenwasser, and Lorraine Iacovitti. 2015. “Neurogenesis Is Enhanced by Stroke in Multiple New Stem Cell Niches along the Ventricular System at Sites of High BBB Permeability.” Neurobiology of Disease 74: 229.

We found that both stroke and bFGF induce a dramatic and long-lasting (14 day) rise in the proliferation NSCs capable of differentiating into glial progenitors, astrocyte progenitors and neurons in both the SVZ and CVOs. Additionally, all brain niches were shown to contain a rich vasculature with a blood-brain-barrier (BBB) that is highly permeable to systemically injected sodium fluorescein after stroke.

Bennett, Lori, Ming Yang, Grigori Enikolopov, and Lorraine Iacovitti. 2009. “Circumventricular Organs: A Novel Site of Neural Stem Cells in the Adult Brain.” Molecular and Cellular Neuroscience 41 (3): 337.

For the first time, we showed that in adult rat and mouse, the circumventricular organs (CVOs) are rich in neural stem cells which can proliferate and undergo constitutive neurogenesis and gliogenesis, similar to classic stem cell niches (SVZ, SGZ). With the discovery of novel stem cell niches along the entire neuraxis, these pioneering studies have re-written dogma, establishing for the first time the potential for widespread neurogenesis and gliogenesis throughout the adult brain.

Iacovitti, Lorraine, Angela E. Donaldson, Cheryl E. Marshall, Sokreine Suon, and Ming Yang. 2007. “A Protocol for the Differentiation of Human Embryonic Stem Cells into Dopaminergic Neurons Using Only Chemically Defined Human Additives: Studies in Vitro and in Vivo.” Brain Research 1127 (1): 19.

We developed a protocol to efficiently differentiate human embryonic stem cell lines into dopaminergic neurons. Furthermore, the transplanted dopaminergic progenitors develop dopaminergic traits 2-3 weeks later in PD rat models.

Kessler, Mark A, Ming Yang, Kandace L Gollomp, Hao Jin, and Lorraine Iacovitti. 2003. “The Human Tyrosine Hydroxylase Gene Promoter.” Brain Research. Molecular Brain Research 112 (1–2): 8.

We isolated 13kb of the single copy human tyrosine hydroxylase (hTH) gene and generated an transgenic mouse line using GFP reporter gene driven by this promotor. Our work demonstrated for the first time the ability of a human TH promoter sequence to direct GFP expression to TH+ neurons of the substantia nigra and other TH+ brain regions. These TH reporter mice have been shared with colleagues around the world.