Chemical factors induce aggregative multicellularity in a close unicellular relative of animals

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Abstract

Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals’ closest unicellular living relatives—the filasterean Capsaspora owczarzaki . We discovered that Capsaspora aggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viable Capsaspora cells. We also found that this multicellular stage is reversible as depletion of the cues triggers disaggregation, which can be overcome upon reinduction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.

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  1. 20 minutes after addition of 10% (v/v) FBS

    Curious if you also see this effect if you add additional FBS to cells that were grown in media already containing FBS? Or is it unique to cells that haven't yet "seen" FBS?

  2. whole lipoprotein particles

    As someone who doesn't think about LDLs very much, it could be super useful to give a little more of an explanation of the difference here and what one might expect your whole particles to contain. Maybe a schematic? I'm worried that I'm missing something.

  3. Therefore, one or more of the polar lipids of LDLs appear to305be the true aggregation cue

    This is super interesting. I think I am missing something though - why do you think the proteolytic degradation of your fraction earlier in the study led to the destroying of aggregation activity? Is this because the protein(s) were required for assembly LDLs in the first place?

  4. not343simply a “glue” that links passive cells together. Instead, LDLs likely induce aggregation344through an active biological response

    This is cool. I also found this way of explaining it really clear/helpful. Presumably there are advantages to this strategy too - allowing Capsaspora to respond to a diversity of cues through response mechanisms so they aren't strictly dependent on the molecular cues themself for the downstream consequences. Would be really interesting to see how promiscuous this response is to different kinds of LDLs.

  5. Additionally, aggregation may be induced by other polar lipids that are not420prevalent in LDLs but are ubiquitous in bacterial membranes (e.g., phosphatidylglycerols,421phosphatidylethanolamines, cardiolipins).

    that's an interesting thought

  6. chemically regulated aggregation,

    why do you think Capsaspora has evolved the requirement of two molecules, and not just one? What does the simultaneous presence of these two chemical factors represent in its environment, and what advantages does it provide to have two different knobs that can be tuned?

  7. chemically regulated aggregation,

    why do you think Capsaspora has evolved the requirement of two molecules, and not just one? What does the simultaneous presence of these two chemical factors represent in its environment, and what advantages does it provide to have two different knobs that can be tuned?

  8. Additionally, aggregation may be induced by other polar lipids that are not420prevalent in LDLs but are ubiquitous in bacterial membranes (e.g., phosphatidylglycerols,421phosphatidylethanolamines, cardiolipins).

    that's an interesting thought

  9. not343simply a “glue” that links passive cells together. Instead, LDLs likely induce aggregation344through an active biological response

    This is cool. I also found this way of explaining it really clear/helpful. Presumably there are advantages to this strategy too - allowing Capsaspora to respond to a diversity of cues through response mechanisms so they aren't strictly dependent on the molecular cues themself for the downstream consequences. Would be really interesting to see how promiscuous this response is to different kinds of LDLs.

  10. Therefore, one or more of the polar lipids of LDLs appear to305be the true aggregation cue

    This is super interesting. I think I am missing something though - why do you think the proteolytic degradation of your fraction earlier in the study led to the destroying of aggregation activity? Is this because the protein(s) were required for assembly LDLs in the first place?

  11. whole lipoprotein particles

    As someone who doesn't think about LDLs very much, it could be super useful to give a little more of an explanation of the difference here and what one might expect your whole particles to contain. Maybe a schematic? I'm worried that I'm missing something.

  12. 20 minutes after addition of 10% (v/v) FBS

    Curious if you also see this effect if you add additional FBS to cells that were grown in media already containing FBS? Or is it unique to cells that haven't yet "seen" FBS?