Thesis live 1.1 The stem cell niche

In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.

1.1 Stem cells and regenerative medicine

The concept of the stem cell niche was first proposed theoretically by Schofield exactly 30 years ago in the context of hematopoietic stem cells: “a hypothesis is proposed in which the stem cell is seen in association with other cells which determine its behaviour. It becomes essentially a fixed tissue cell. Its maturation is prevented and, as a result, its continued proliferation as a stem cell is assured. Its progeny, unless they can occupy a similar stem cell ‘niche’, are first generation colony-forming cells, which proliferate and mature to acquire a high probability of differentiation, i.e., they have an age-structure.”

Niches are restricted and specialized tissue microenvironments that integrate local and systemic signals for the regulation and maintenance for resident stem cells. The elements of the stem cell niche include the constraints of the architectural space, cellular components like stromal supporting and descendent/progenitor cells and acellular elements, like soluble and membrane bound molecules, paracrine and endocrine signals from local or distant sources and neural input [Figure by Jonas].

Niches are dynamic entities, could be redistributed and ideally “a candidate niche

Thesis live: 1.2 tissue/stem cell introduction scheme

In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.

When producing a text, a post my building strategy is not linear, but heavily non-linear (I wouldn’t say it’s circular): I’d like to jump to the part of the story where there is something instantly to write/edit; be it the beginning, middle or end. In case of scientific articles frequently the first part to be build are figures/methods, which forms the bulk, the middle of the story after introduction, before discussion.

1.2. Tissues, organs with different turnover and regenerative potential

In order to discuss the different adult tissues in a unified manner, from a systemic point of view, I use the following tissue/stem cell introduction scheme where data are available: development of particular tissue, number of cell types, bioenergetics (high/intermediate/low energy demand), turnover (high/intermediate/low), regenerative potential (high/intermediate/low), resident stem cells, niche, markers, cell sources from other tissues that can contribute to the particular tissue during normal turnover or chronic/acute injury.

Thesis live: Introduction, “contents” draft

From now on I start every “thesis live” post with the standard introduction: In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential

I am not aiming any perfection, my focus is clearly on getting things (the PhD) done here. Anyway, I found the idea of “writing” a complete, lengthy and formal thesis outdated and inefficient (after all, scientists should conduct nice experiments and publish their results in short, inforich and accessible research papers in order to share it ASAP with the research community, not in book-length, otherwise unaccessible PDFs) and so I try to keep myself motivated by

- doing this “thesis live” series as an open science experiment and getting useful feedback from my fellow scientists and readers

- trying to include as many systemic, whole body level material into it that could be relevant for systemic regmed approaches

- reminding myself every day that without a PhD it is hard to move further in science officially (that’s the least motivating factor though as it is official)

After the blah-blah let’s start with the planned introduction points:

1. Introduction:

1.1 Stem cells and regenerative medicine

1.2. Tissues, organs with different turnover and regenerative potential

Gut epithelium,
Blood - hematopoietic system
Epidermis,
Mammary epithelium,
Vascular endothelium,

Warming up to write my thesis on the blog

Not much happened since my announcement on Editing my doctoral thesis on stem cells in a blog: Why not?. I went to the U.S. first and started doing research instead of finishing my PhD education. But now I am back in this “getting a PhD” business as in January I passed the prerequisite comprehensive stem cell and mitochondrial biology exam with a plus.

Will JoVE’s new science blog service reinvent the genre?

The pioneer biological video publishing site JoVE (covered here many times) will soon launch a blogging platform and a community site. Nikita Bernstein, the main nerd behind JoVE is building the code and the platform - as Anne Kushnir informed me - should hopefully go live in the next couple of weeks. At least that is what can be known publicly.
The expectations are high and the JoVE guys (co-founders Moshe Pritsker and Nikita) themselves raised the bar with the quality and concept of video-protocols. As JoVE is a startup, not an established company with big inertia, they could be experimental but within the limits of their investors’ patience and money.

The real question for me whether JoVE’s blogging service can renew the genre of science blogging or at least bring a previously non-existing color into it? Points:

- Who will become JoVE’s first generation bloggers? Fresh blood? If yes what will be the source? Senior scientists, high school students, postdocs in the U.S.A., discovering the web?

- Existing bloggers who’d like to syndicate their content? Bloggers from Scienceblogs, Nature Network or from the DNA Network? Independent bloggers from outside theses established circles? Journalists? What will be the bait? For existing bloggers, who are tempted to commercialize their activity somehow the crucial question is whether they can generate any revenue out of this new platform? Will they be paid by traffic, and if yes how competitive are the tariffs? Is it possible to install paid ads, banners on the blogs and the bloggers could be paid based on pay per click methods just like Google AdSense?

- What about content rights? Exclusive, non-exclusive, et cetera? Would there be any topic restrictions? How can quality science blogging and credit is maintained in the long term?

The Spittoon: the eminent corporate blog of 23andMe and Consumer Enabled Research

The personal genomics service 23andMe just launched publicly a corporate blog called The Spittoon that has been internally up for a few weeks. It is a new chapter in biotech corporate blogging. Just like the web page of 23andMe, The Spittoon’s WordPress blog platform, the concept and design is excellent: amongst others you can find scientific blog posts written by Matt Crenson science writer and posts written by founders Linda Avey and Anne Wojcicki in the name of radical transparency. As Wired fellow Clive Thompson wrote:

Radical forms of transparency are now the norm at startups - and even some Fortune 500 companies. It is a strange and abrupt reversal of corporate values. Not long ago, the only public statements a company ever made were professionally written press releases and the rare, stage-managed speech by the CEO. Now firms spill information in torrents, posting internal memos and strategy goals, letting everyone from the top dog to shop-floor workers blog publicly about what their firm is doing right - and wrong. Jonathan Schwartz, the CEO of Sun Microsystems, dishes company dirt and apologizes to startups he’s accidentally screwed. Venture capitalists now demand that CEOs be fluent in blogspeak.

Radical transparency could be standard in the case of Silicon Valley tech startups but in the Biotech Industry the standards are light years away from that. For instance the 23andMe research team communicates publicly on the biparental inheritance of mitochondrial DNA which is a sensitive issue concerning their genealogy service. The reason why Spittoon is so web-friendly and uptodate and is in fact a paradigm corporate blog for every other biotech company in the future is its web-based business model and Google-like corporate culture thanks to its networking background.

For instance, Anne Wojcicki co-founder introduces the concept of Consumer Enabled Research in her introductory blog post The Power of We:

Our goal at 23andMe is to enable individuals to form communities around shared interests and to empower those communities to be actively involved with research. We call it Consumer Enabled Research. We don’t just want communities to have a voice, we want to provide a platform for them to collectively aggregate their genetic information. One of the significant bottlenecks in research is the lack of data. Researchers and physicians rarely have enough of it to really understand a disease or how to treat it. Our goal is to change that.

After registration readers can make comments and I strongly hope that the comment system will not be shut down (just like in the past at BoingBoing), but for that commenters should be on-topic and moderate. I’ve just commented Wojcicki’s post, but I’d like to share it with you here too:

My transatlantic air reading: Bubble City, a blog novel by Aaron Swartz

At least I know what I will read on the plane over at the Atlantic tomorrow back to old Europe: Bubble City by Aaron Swartz. What by who? Bubble city is a blog tech novel with chapters as posts. The story takes place in San Francisco and the Silicon Valley around a startup called Newsflip going deep into current web techniques, startup happenings, Google trends & types and tokens of people with the tools of fiction. It is well written, it is witty, I’ve just started but quickly became excited about it due to its experimental character and the insider angle of the writer behind. Bubble City is the brainchild of Aaron Swartz Reddit cofounder, who is an extremely talented 20 year old American programmer, hacker (think of George Hotz or young Saul Kripke tinkering with modal logics), although in his blog Raw Thought (long time blogroll guest of Pimm) he usually writes like an old central European, highbrow human intellectual with the necessary cultural references. And that makes him a very interesting phenomenon, one that is almost missing in the American tech-web scene: an intellectual with a broad spectrum of interests and arguments. I met Aaron at the last seconds of the SciFoo Camp at the Googleplex (he writes a lot about the Number One Plex) and really liked his celebrity focused gossip liveblogging account on the event with people like Tim O’ Reilly and Henry Gee explaining themselves in the comment section.

Hopefully Aaron will be able to finish Bubble City by excluding or neutralizing or properly incorporating outworld reflexion (like this and that of Blogoscoped) into it. Finishing a novel and completing a code are not the same though and epic talent has the bad habit not to let young writers reach perfection in their early trials.

Here are 2 sections from Bubble city and the links to the 11 chapters so far (it is not aggregated as far as I know and you always have to change the numbers at the end of the URL):

Chapter 1

He popped open the recording software, making sure he got his nose squarely in its frame, his face so close that spittle would land on the lens. In a world where every teenage kid could stream a live feed of himself having sex to millions, only the most aggressive vlogcasters survived. Wayne was no dummy. He didn’t get to be the number seven blog in the TechnoScene rankings by sitting back and offering his opinions. No. This was war and every show a battle.

Today’s enemy? Newsflip, one of the crummy little online news aggregator sites, which was threatening to write him out of the history books by dumping the technology he’d single-handedly invented, news notation analysis (NNA), and going with some upstart competitor that didn’t even bother to have an acronym for a name. Sure, Newsflip was a tiny site in the scheme of things, but if it switched it would set a dangerous precedent.

Chapter 2

Downtown San Francisco is a world of carefully-gridded streets and looming skyscrapers, but hidden behind a gas station on Third is a place that almost looks like another world. The sun shines brightly upon a park with green grass and tall shady trees and vibrant swings with children. The park is an oval and the perimeter is lined with small, pastel-colored buildings. Here and there are a smattering of small cafes and restaurants. And the other buildings are filled with startups. Twitter here. Adaptive Path there. Even Yahoo, when it wanted to encourage its employees to be more startup-y, opened up an office in the neighborhood. Sit on the grass and chances are you’ll sit near a friend from another company or bump into them in line at a cafe. The place crawls with companies and back on the street, surveying the scene with a distant but watchful eye, lie the journalists, whose publications cover with awe the rumblings of those below. It was here that Newsflip made its home.

What is your (science) blogging writing style, Deepak Singh?

Actually the idea of asking science bloggers about their style came to my mind reading one email remark of Deepak on the writing style. Deepak is the guy behind business/byte/genes/molecules and he was a Sci Foo camper this year. He is one amongst the few bloggers who are standing at the intersection of science and technology and being the founder of Bioscreencast he is actively experiencing the life of a bioweb entrepreneur.

My style is a heady mix of spontaneity, continuous partial attention, a total lack of time, the random connection of ideas formed at different times, semi-formal essay-style writing, attempts at humor, deep thought, tempered enthusiasm, and unbridled passion.

Wired style SENS3 conference intro or be aware of your audience

As this very site here is embedded in the blog medium, we could and should be experimental and eclectic in our style as we cannot control (just target) our audience, thank the web. Now a report on a science conference could be addressed to very different audiences, and yesterday I showed an example on how to present an unconventional science conference to the mainstream science establishment. But if I’d like to target, say, the geeky-layman Wired audience, than I should find another angle on the SENS3 conference which is not restricted to the science content but highlights the inconvenience around it. (Just take a look on how journalists at the Wired Science blog are considering to cover their subject.) Say the story would look like this:

Summary (Lead): A recent unconventional strategic conference on translational science in ageing related damages and diseases shows the benefits of mixing the traditionally homogeneous audience of science conferences with visitors from outside science in order to gain new insights, and put ageing and lifespan extension in a broader cultural context.

First paragraph: Question: Which science conference has such a variety of participants that includes hardcore life scientists from top-notch universities, entrepreneurially inclined benefactors, former IT professional turned bioinformaticians, practicing life extensionists, high school talents, fitness fanatics, lawyers, and even a Hollywood scriptwriter, or an investment banker turned biology student due to a recent cancer survival? Answer: The SENS3 conference in Cambridge.

Compare this to that:

Mr. Gunn’s dissertation on blog: Investigating the role of MSCs in repair of bone

Mr Gunn’s thesis is in a far more advanced stage, and even nerdier than mine. 

Choosing a proper title for the thesis: The physiologic role of stem cells…

In my last “live” thesis post I said that the first steps of building a thesis are: figuring out a unifying concept behind all my experimental work and finding a proper thesis title.

During my PhD work I’ve done various stem cell transplantations (local and systemic) into brain, heart, muscle tissues using different stem cell sources, just like freshly isolated bone marrow derived cells (hematopoietic, mesenchymal stem cells), murine embryonic stem cells, cultured hematopoietic stem cells. And I was heavily involved in the mechanisms by which exogenous stem cells can contribute to host tissues and the way these exogenous cells and lesion models can motilize the built in endogenuous stem and progenitor cell populations. So for me the unifying concept behind is a kind of systemic approach, that is to collect many stem cell data from various tissues, organs, compare them to each other and derive some unifying principles from them that could be adapted to other tissue environments too. And I really would like to introduce some systemic point of view into stem cell biology and regenerative medicine.

Next is finding a proper title for the thesis which embraces the systemic concept, simple but scientific enough to be approved by the academic people. Also it must be broad enough and not too restricted.

My first, rough idea was: Stem cells‘ regenerative mechanisms in tissues with different regenerative potential (turnover)

Uncensored gmail chat between 2 science bloggers on adult issues

me: Hi Bora, can you send me the Nature piece on the Blogging Anthology?
I am not in the Institute and do not have subscription
http://www.nature.com/nature/journal/v447/n7146/full/447779b.html
Sent at 8:58 PM on Wednesday
me: cheers
Bora: No problem. Thanks.
me: wait that is some old stuff.
Published online: 22 January 2007; | doi:10.1038/news070122-I’ve read that
I have in mind the current one: Bloggers unite p779
Paul Stevenson reviews The Open Laboratory: The Best Writing on Science Blogs 2006
doi:10.1038/447779b
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