Max Heiman
@heiman.bsky.social
Associate Professor of Genetics
Harvard Medical School, Boston Children's Hospital
It should be fun, or what's the point?
http://heimanlab.com
Harvard Medical School, Boston Children's Hospital
It should be fun, or what's the point?
http://heimanlab.com
Finally, we used regulatory network analysis to find transcription factors (TFs) with targets enriched among pulsatile genes.
We found some old friends that are known to control larval timing, like blmp-1, nhr-23, and nhr-25, as well as new suspects who might merit further investigation!
We found some old friends that are known to control larval timing, like blmp-1, nhr-23, and nhr-25, as well as new suspects who might merit further investigation!
September 7, 2025 at 1:45 PM
Finally, we used regulatory network analysis to find transcription factors (TFs) with targets enriched among pulsatile genes.
We found some old friends that are known to control larval timing, like blmp-1, nhr-23, and nhr-25, as well as new suspects who might merit further investigation!
We found some old friends that are known to control larval timing, like blmp-1, nhr-23, and nhr-25, as well as new suspects who might merit further investigation!
This implies that the cuticle is not a homogeneous mesh at all, but a patchwork that is stitched together from totally different, cell-type-specific components.
September 7, 2025 at 1:45 PM
This implies that the cuticle is not a homogeneous mesh at all, but a patchwork that is stitched together from totally different, cell-type-specific components.
But a surprise to me was how little overlap there was between cell types. For example, although many cells are making collagens, they're making DIFFERENT collagens. Same with most genes.
In fact, almost half the pulsatile genes we identified were oscillatory in only a single cell type!
In fact, almost half the pulsatile genes we identified were oscillatory in only a single cell type!
September 7, 2025 at 1:45 PM
But a surprise to me was how little overlap there was between cell types. For example, although many cells are making collagens, they're making DIFFERENT collagens. Same with most genes.
In fact, almost half the pulsatile genes we identified were oscillatory in only a single cell type!
In fact, almost half the pulsatile genes we identified were oscillatory in only a single cell type!
Using these new tools, we could ask what kinds of genes oscillate in glia, or skin, or pharynx. For glia and skin it turns out it's mostly #aECM - lots of collagens, ZP domain proteins, and other cuticle proteins. Pharynx has a different kind of cuticle and its oscillatory genes reflect that.
September 7, 2025 at 1:45 PM
Using these new tools, we could ask what kinds of genes oscillate in glia, or skin, or pharynx. For glia and skin it turns out it's mostly #aECM - lots of collagens, ZP domain proteins, and other cuticle proteins. Pharynx has a different kind of cuticle and its oscillatory genes reflect that.
We also developed statistical approaches to quantify how "pulsatile" each gene is within each cell type -- that is, how sharply its expression peaks at one point in time.
September 7, 2025 at 1:45 PM
We also developed statistical approaches to quantify how "pulsatile" each gene is within each cell type -- that is, how sharply its expression peaks at one point in time.
We developed quantitative methods to measure how phased each cell is and how oscillatory each cell type is.
We found that cuticle-producing cell types like socket glia, seam cells, and pharynx epithelia are highly oscillatory, while non-cuticle-producing ones like neurons and muscle are not.
We found that cuticle-producing cell types like socket glia, seam cells, and pharynx epithelia are highly oscillatory, while non-cuticle-producing ones like neurons and muscle are not.
September 7, 2025 at 1:45 PM
We developed quantitative methods to measure how phased each cell is and how oscillatory each cell type is.
We found that cuticle-producing cell types like socket glia, seam cells, and pharynx epithelia are highly oscillatory, while non-cuticle-producing ones like neurons and muscle are not.
We found that cuticle-producing cell types like socket glia, seam cells, and pharynx epithelia are highly oscillatory, while non-cuticle-producing ones like neurons and muscle are not.
We had shown that glia make the cuticle #aECM around neuronal cilia. So, we wondered if loops were a transcriptional cycle tied to cuticle synthesis.
We used expression data from @labgrosshans.bsky.social to color-code each cell based on when in the larval stage its genes are expressed. Bingo!
We used expression data from @labgrosshans.bsky.social to color-code each cell based on when in the larval stage its genes are expressed. Bingo!
September 7, 2025 at 1:45 PM
We had shown that glia make the cuticle #aECM around neuronal cilia. So, we wondered if loops were a transcriptional cycle tied to cuticle synthesis.
We used expression data from @labgrosshans.bsky.social to color-code each cell based on when in the larval stage its genes are expressed. Bingo!
We used expression data from @labgrosshans.bsky.social to color-code each cell based on when in the larval stage its genes are expressed. Bingo!
In our study, we had begun by trying to do single-cell transcriptomic analysis of C. elegans glia.
But, we kept getting loopy patterns in PCA space, like this:
But, we kept getting loopy patterns in PCA space, like this:
September 7, 2025 at 1:45 PM
In our study, we had begun by trying to do single-cell transcriptomic analysis of C. elegans glia.
But, we kept getting loopy patterns in PCA space, like this:
But, we kept getting loopy patterns in PCA space, like this:
This opens up (literally) a lot of possibilities! I thought the eggshell was needed as a mechanical constraint for morphogenesis. This image of a comma stage embryo happily letting it all hang out in the world with nothing around it is wild!
June 27, 2025 at 8:35 PM
This opens up (literally) a lot of possibilities! I thought the eggshell was needed as a mechanical constraint for morphogenesis. This image of a comma stage embryo happily letting it all hang out in the world with nothing around it is wild!
You will enjoy these hand-drawn tracings from Brenner's notebooks! I would have liked to include them in the intro but it would have been getting a little too historical.
libgallery.cshl.edu/items/show/7...
libgallery.cshl.edu/items/show/7...
June 9, 2025 at 6:27 PM
You will enjoy these hand-drawn tracings from Brenner's notebooks! I would have liked to include them in the intro but it would have been getting a little too historical.
libgallery.cshl.edu/items/show/7...
libgallery.cshl.edu/items/show/7...
In 1975 "Bohemian Rhapsody" and "Space Oddity" were on the UK top 100, and Ward, Thomson, White, and Brenner published the first reconstruction of the C. elegans sensory anatomy.
A short 50 years later, we reconstructed the same neurons and glia in the embryo:
doi.org/10.1101/2025...
A short 50 years later, we reconstructed the same neurons and glia in the embryo:
doi.org/10.1101/2025...
June 9, 2025 at 11:11 AM
In 1975 "Bohemian Rhapsody" and "Space Oddity" were on the UK top 100, and Ward, Thomson, White, and Brenner published the first reconstruction of the C. elegans sensory anatomy.
A short 50 years later, we reconstructed the same neurons and glia in the embryo:
doi.org/10.1101/2025...
A short 50 years later, we reconstructed the same neurons and glia in the embryo:
doi.org/10.1101/2025...
I took my son and his friend to @wgbh.org 's High School Quiz Show. It is super fun (and free)! It aired this week & you can see us for a nanosecond.
As a bonus, the winning coach turned out to be the husband of a @senguptalab.bsky.social grad student whose defense I was on several years ago!
As a bonus, the winning coach turned out to be the husband of a @senguptalab.bsky.social grad student whose defense I was on several years ago!
May 24, 2025 at 1:22 AM
I took my son and his friend to @wgbh.org 's High School Quiz Show. It is super fun (and free)! It aired this week & you can see us for a nanosecond.
As a bonus, the winning coach turned out to be the husband of a @senguptalab.bsky.social grad student whose defense I was on several years ago!
As a bonus, the winning coach turned out to be the husband of a @senguptalab.bsky.social grad student whose defense I was on several years ago!
photo from lab tonight, courtesy of grad student Jung Hyun Yoo
April 16, 2025 at 12:47 AM
photo from lab tonight, courtesy of grad student Jung Hyun Yoo
I need a new assistant, this one has an attitude and his emails make no sense.
February 26, 2025 at 12:41 PM
I need a new assistant, this one has an attitude and his emails make no sense.
You may have more experience than I do! I like NIGMS's explainer:
"-Breakthroughs emerge from... fundamental knowledge contributed by many people over many years
-Supporting a broad and diverse scientific portfolio maximizes the chances for breakthroughs"
Do you find patients can't get that?
"-Breakthroughs emerge from... fundamental knowledge contributed by many people over many years
-Supporting a broad and diverse scientific portfolio maximizes the chances for breakthroughs"
Do you find patients can't get that?
January 27, 2025 at 12:51 AM
You may have more experience than I do! I like NIGMS's explainer:
"-Breakthroughs emerge from... fundamental knowledge contributed by many people over many years
-Supporting a broad and diverse scientific portfolio maximizes the chances for breakthroughs"
Do you find patients can't get that?
"-Breakthroughs emerge from... fundamental knowledge contributed by many people over many years
-Supporting a broad and diverse scientific portfolio maximizes the chances for breakthroughs"
Do you find patients can't get that?
for those (like me) who didn't get the joke at the end of the thread.
January 26, 2025 at 7:00 PM
for those (like me) who didn't get the joke at the end of the thread.
and a chappy chanukah too
December 25, 2024 at 10:31 PM
and a chappy chanukah too
File under "Reasons to live in New England"
December 21, 2024 at 12:15 AM
File under "Reasons to live in New England"
Wishing you, as my tweens say, a Merry Rizzmas
December 20, 2024 at 11:46 PM
Wishing you, as my tweens say, a Merry Rizzmas
It is an exciting time to work on cilia!
Join us 5 pm Sun at #cellbio2024 to talk about new roles for cilia in neuron-glia communication, as cellular transmitters, and even in chromosome segregation in meiosis!
"Cilia in native habitats and novel
contexts" 5-6:30 pm Sun Dec 15, Room 28C
Join us 5 pm Sun at #cellbio2024 to talk about new roles for cilia in neuron-glia communication, as cellular transmitters, and even in chromosome segregation in meiosis!
"Cilia in native habitats and novel
contexts" 5-6:30 pm Sun Dec 15, Room 28C
December 12, 2024 at 2:38 PM
It is an exciting time to work on cilia!
Join us 5 pm Sun at #cellbio2024 to talk about new roles for cilia in neuron-glia communication, as cellular transmitters, and even in chromosome segregation in meiosis!
"Cilia in native habitats and novel
contexts" 5-6:30 pm Sun Dec 15, Room 28C
Join us 5 pm Sun at #cellbio2024 to talk about new roles for cilia in neuron-glia communication, as cellular transmitters, and even in chromosome segregation in meiosis!
"Cilia in native habitats and novel
contexts" 5-6:30 pm Sun Dec 15, Room 28C
Oh, I keep everything. I've been incredibly privileged in my teachers (and students!). Cell bio from Joel Rosenbaum? Genetics from Cori Bargmann, Cynthia Kenyon, Andrew Murray, and Ira Herskowitz? It's nuts. Although some of Ira's humor went over my head. ("Memorize - note similarity to alphabet!")
December 9, 2024 at 3:08 PM
Oh, I keep everything. I've been incredibly privileged in my teachers (and students!). Cell bio from Joel Rosenbaum? Genetics from Cori Bargmann, Cynthia Kenyon, Andrew Murray, and Ira Herskowitz? It's nuts. Although some of Ira's humor went over my head. ("Memorize - note similarity to alphabet!")
Glad you were not my grader!
December 9, 2024 at 1:58 PM
Glad you were not my grader!