Zehao-Tommy Zhang

Lineage recording in monoclonal gastruloids reveals heritable modes of early development Mammalian stem cells possess a remarkable capacity for self-organization, a property that underlies increasingly sophisticated in vitro models of early development. However, even under carefully contr...

New preprint with the Shendure lab @jshendure.bsky.social ! We apply the DNA Typewriter lineage recorder to mouse 3D gastruloids, a powerful model of early mammalian development. Led by Sam Regalado and CX Qiu @cxqiu.bsky.social : www.biorxiv.org/content/10.1... (1/13)

This work wouldn't have been possible without the CR samples & generous support from NIH and NIA, and crucial funding from Stavros Niarchos Foundation and Kellen Women’s Entrepreneurship Fund, Center for Integrated Cellular Analysis & AFAR. Thank you all!

Alex, Chloe & I are deeply grateful for the incredible support from all co-authors @junyuecao.bsky.social ’s lab & @rockefelleruniv.bsky.social !

Looking ahead, we're keen to apply our scalable & low-cost EasySci & IRISeq methods to diverse aging interventions and across species, with the goal in mind to uncover evolutionarily conserved and broadly applicable cellular and molecular targets to promote healthy aging for all.

A key limitation: we studied only male mice & are excited to see if female samples show similar/different effects!

Our study offers a deep atlas of CR's impact on the aging mouse brain. We are excited to further explore if CR modulates aging cell population dynamics through inter-cellular signaling OR by direct action on aging-associated cells.

CR also takes a swing at cellular senescence! With IRISeq, We observed a significant reduction in senescence-associated gene expression across various brain regions and cell types upon CR.

Intriguingly, CR’s boost to neurogenesis is time-sensitive! 🕰️ It helps preserve neurogenic cell populations (stem cells & neuroblasts) earlier in life (e.g., at 12 months), delaying their depletion. However, this effect wasn't sustained at much later time points (18 & 24 months).

CR significantly counteracts the age-related expansion of disease-associated glial cells. We observed a striking reduction in inflammatory cell states like disease-associated microglia & oligodendrocytes – pointing to CR’s power to dampen brain inflammation.

A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains - Nature Genetics Single-cell transcriptomes and single-cell chromatin accessibility profiles generated using EasySci provide a global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics in h...

We previously proposed that altered cell population dynamics play an essential role in brain aging and could serve as treatment targets (www.nature.com/articles/s41...). Now, with >500K cells profiled, we see how CR directly remodels these dynamics!

The precise cellular & regional mechanisms of CR's benefits to the aging brain have been elusive. To bridge this gap, we brought cutting-edge tech – highly scalable single-nuc(EasySci) & spatial transcriptomics (IRISeq, kudos to Abdul & Weirong) – to dissect this age-old yet resilient strategy.

Spatiotemporal profiling reveals the impact of caloric restriction on mammalian brain aging Aging induces functional declines in the mammalian brain, increasing its vulnerability to cognitive impairments and neurodegenerative disorders. Among various interventions to slow the aging process, ...

But how does it truly work on the aging brain? We investigated! 🧠 www.biorxiv.org/content/10.1...

Why do many aging interventions come & go, yet Caloric Restriction (CR) remains a robust pillar, extending healthspan across species? Its benefits are even noted in ancient eastern texts like The Yellow Emperor’s Classic of Internal Medicine!

The 15‐Year Survival Advantage: Immune Resilience as a Salutogenic Force in Healthy Aging Human aging shows puzzling diversity: similar aging rates yet vastly different health outcomes. Our study of ~17,500 people revealed a health-promoting trait (more common in women) linked to strong i....

The importance of the immune system for healthy aging.
A large multi-cohort study identifies a mechanism of immune resilience with substantial impact for outcomes
onlinelibrary.wiley.com/doi/10.1111/...

Today we report the directed evolution of HUH into rHUH, a sequence-specific covalent protein tag for RNA labeling. rHUH was hard to engineer: the initial HUH template had no RNA activity, so we started with RNA-DNA hybrids. 30 rounds of selection on the yeast surface were required, and 7 cycles of

Biological sex matters in brain aging

Biological sex is a key modifier of #aging phenotypes, including #Brain 🧠 aging.
See this piece out today in #Neuron, spearheaded by @denadubal.bsky.social, co-authored by #YousinSuh, @ctmurphy1.bsky.social and myself on the topic:
www.sciencedirect.com/science/arti...
#GeroSky #SexDifferences

Interested in brain aging? We are super excited to share our new review!!

"Brain aging and rejuvenation at single-cell resolution" 🧪🧠

Massive CONGRATS to Eric Sun, Rahul Nagvekar, and Angie Pogson, three phenomenal graduate students in the lab!!

authors.elsevier.com/sd/article/S...

Thank you Szen!!

Study reveals how unexpected shifts in cell populations are revising our understanding of the aging process - News A newly created atlas of 21 million cells could provide fresh directions for anti-aging therapies.

A newly created atlas of 21 million cells from @junyuecao.bsky.social's lab led by @tommyz626.bsky.social could upend long-held assumptions about how we age and provide fresh directions for anti-aging therapies. #RockefellerScience

Joined @junyuecao.bsky.social's lab without knowing single-cell genomics - after 3 years of failing, crying, learning, and growing, I’m proud to share the PanSci! Huge thanks to amazing mentors Jun & Wei and support from @rockefelleruniv.bsky.social. The secrets of aging are starting to unfold!