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.

Jacon Hanna Lab

Stem Cell Studies

Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. We found an expert in this field named Jacob Hanna from the Jacob Hanna Lab.

 

Focus on Pluripotent Stem Cell Studies and Epigenetic ReprogrammingDr Jacob Hanna

The research being done at Jacob Hanna Lab zeroes in on investigating cellular reprogramming processes which involve generating induced pluripotent stem cells from somatic cells. Reprogramming requires eliminating and remodeling epigenetic marks like DNA methylation. By using exogenous small molecules or transcription factors, epigenetic reprogramming can be artificially induced. This will create induced pluripotent stem cells that can be used for biomedical and stem cell therapy research, without the need of embryos.

 

More About Stem Cell Research
They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adultorganisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells— ectoderm, endoderm and mesoderm (see induced pluripotent stem cells)—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three known accessible sources of autologous adult stem cells in humans:

  1. Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest).
  2. Adipose tissue (lipid cells), which requires extraction by liposuction.
  3. Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.

Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one’s own body, just as one may bank his or her own blood for elective surgical procedures.

Adult stem cells are frequently used in various medical therapies (e.g., bone marrow transplantation). Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies.