Jacob Hanna / Jacob Hanna Lab

Direct Cell Reprogramming

Research Findings at the Lab

Understanding Cellular Reprogramming by Jacob Hanna

In 2006, a development was made that makes it possible for scientists to reverse cellular differentiation and produce induced pluripotent cells via epigenetic reprogramming of somatic cells. The Jacob Hanna Lab is at the forefront of exploring the spectacular changes that occur in the cells during epigenetic reprogramming and knowing how these molecular changes can be related to in-vivo procedures.

The lab has already pinpointed two chromatin regulators that are vital in epigenetic reprogramming. One chromatin is key in the process, while the other multi-component complex is described as an obstacle which, if removed, could make reprogramming faster and better synchronized.

Working Out Naïve and Primed Pluripotent States

Pluripotent cells can be found in either naïve or primed state. Naïve pluripotent state is established in mature blastocyst. Primed pluripotent state, on the other hand, is established in the post-implantation epiblast. Only naïve cells can meaningfully contribute to the chimera or organism made up of genetically different cells.

The lab takes a closer look at how naïve and primed pluripotent cells are regulated both in mice and humans. Firstly discovered by Hanna lab, scientists are now able to maintain the naïve condition of human pluripotent cells, which can greatly benefit research on cross-species chimeric embryos in mice and potentially other animals. Present efforts on this matter also focus on shedding light on naïve and primed cellular states across multiple species.

Cross-Species Chimerism in Human and Mouse

At Jacob Hanna Lab, they have found that human stem cells that have been produced in naïve cellular state can be introduced into mouse blastocyst. This finding is instrumental in cross-species chimeric embryos. The result of this investigation may have wide-ranging impact on human disease modeling.

This is the first of a series of featured labs that we will be publishing here on The Stem Cell Podcast website.

The Stem Cell Podcast

This is a preview of Episode 02 of The Stem Cell Podcast

In this episode our science roundup includes novel poop pills, anti-acne bacteria, and Eric Kandel’s RB-AB 48 Alzheimer’s target.

We then get into some hot stem cell papers, including one by Dr. Jacob Hanna’s group recently published in Nature describing a method for 100% reprogramming efficiency. And finally we end with our signature rant about our pathetic government and the shutdown.

The common practice of reprogramming somatic cells to a stem cell state involves introducing four transcription factors: Oct4, Sox2, Klf4, and Myc.  Problem is, there’s another transcription factor lingering in adult cells, and it appears to be the cause of the abysmal reprogramming frequency that has frustrated researchers.

Those four transcription factors that can de-differentiate cells simultaneously recruit the transcriptional repressor Mbd3.  Unfortunately for scientists trying to make stem cells, Mbd3 puts the brakes on reprogramming.  Its job is to keep cells in their differentiated state.  This is an incredibly important job for both successful development and long-term health, but it is at odds with the efforts of stem cell scientists.