Musculoskeletal Stem Cells

For July 24, 2019                              

Please share with your friends and neighbors, especially those interested in stem cells — and muscles.


Hi WN@TL Fans,

For the plant scientists among us, the use of the word “stem cells” by animal biologists can be confusing.  Plants have stem cells because, well, they have stems. Plants also have leaf cells and root cells and flower cells.  In plants, cells all come from meristems:  regions of cells (often at the growing tip of a stem or root) that divide into two cells, with one cell developing into a specific type while the other cell remains undifferentiated and keeps dividing. 

Plants also exhibit a thing called ‘continuous morphogenesis.’  They grow not just by getting bigger, but also by adding new leaves & limbs and new roots and by lengthening stems and sprouting flowers.  Mammals generally don’t do that:  once they’re done with embryogenesis, they pretty much just get bigger without sprouting more limbs or organs.

While plants are generative in cranking out new leaves, adults of animals like humans have to be regenerative in cranking out replacement cells and occasionally replacement tissues and, rarely, replacement organs. 

At WN@TL we’ve had talks on mammalian stem cells of the eye and of the heart.  Now we’ll get a talk on figuring out which kinds of animal cells serve both in embryos and in adults as the stem cells that generate new cells for the muscles that move us and for the connective tissues that keep us together. 

This week (July 24) Deneen Wellik, chair of the Department of Cell & Regenerative Biology, will be here to speak on “Hox Gene Expression and Function in Musculoskeletal Stem Cells.”

Here’s how she describes her talk:

Hox genes were discovered in the 1970s to be a set of genes arranged in a line, in the same order as their expression, on a chromosome of the fruit fly Drosophila.  They play critical roles in patterning the body along its head-to-tail axis.  Remarkably, the loss of function of Hox genes results in “anterior homeotic transformation”:  that is, segments of the mutant flies are transformed into duplications of the previous segment. 

The sequencing of genomes of many model organisms, as well as the discovery of the ability to design gene mutations in mice, permitted researchers to show that the function of these genes in patterning of the embryo is a conserved feature of this set of genes (ie., as it is in the fly, so it is in the mouse).   The loss of function of Hox genes in mammals leads to transformation of regions of the axial skeleton. In vertebrates, these genes were also used to pattern the segment of our forelimbs and hindlimbs.  Thus, loss of Hox gene function leads to dramatic defects in limb skeletal pattern.

Recent work from the laboratory is establishing that these Hox-expressing cells, indeed, serve as a self-renewing stem cell population in the skeleton from the earliest stages of development continuously throughout the life of the animal. 

Further, following the lineage that is produced from these cells at all stages, we demonstrate that Hox-expressing stromal tissue is the source of chondrocytes (cartilage-making cells), osteoblasts (bone cells) and adipocytes (fat cells) in mammals. Critically, Hox genes continue to function in the skeleton throughout life as well.  In more recent work, the laboratory is establishing that these genes control muscle development, regeneration and repair as well.

About the Speaker:

Professor Wellik’s Bio:

I was born and raised in a small town in Missouri – a Midwesterner through and through.  I was the first person from my family to go to college (or even leave that rural area of Missouri for 5+ generations). I did my undergraduate work at Washington University (only ~50 miles away, but another world), then worked as a technician first in STL for a year then at Hazelton (now Covance) here in Madison.

After a few years, I returned to graduate school and did my PhD with Hector DeLuca here in the Biochemistry Department. I worked on retinoids, which in the 90s, were being shown to regulate this fascinating set of genes called Hox genes. My fascination with these genes led me to completely switch fields from chemistry and physiology to developmental genetics. 

I did my postdoctoral work at the University of Utah with Mario Capecchi, who discovered the technology that allowed scientist to perform directed gene targeting in mice (he won the Nobel prize for this in 2007). His laboratory had initiated the use of this new technology to gene target all 39 Hox genes; thus, I entered my postdoc with a plethora of new tools that allowed me to pursue work on these genes.  

I started my own laboratory at the University of Michigan as an Assistant Professor in 2003 and my laboratory has continued to work on Hox gene function in many organ systems (kidney, lung, pancreas, prostate), but we have focused strongly on the musculoskeletal system. 

I moved back to Madison to take the position of Chair of Cell and Regenerative Biology in December of 2018 where we continue our work on these genes and also participate in the Stem Cell and Regenerative Medicine Center, which was a huge draw to me to join UW again. Very happy to be back in Madison.


Next week (July 31) Anne Marie Singh of the Department of Pediatrics will share her insights into the nature and management of food allergies in children.

As someone who started weekly allergy shots in third grade, I’m looking forward to hearing more about what got screwed up in my immune system. 

The shots likely did some good:  I’m not allergic now to anything, with the possible exception of work, but that’s more metaphorical than immunological.

Hope to see you soon at Wednesday Nite @ The Lab.

Thanks again!

Tom Zinnen
Biotechnology Center & Division of Extension