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Articles by Kyle M. Loh
Two parallel neural ectoderm progenitors contribute to the developing brain
Abstract When and how different brain regions diversify from one another remains unresolved. Does a common neural ectoderm progenitor generate the entire brain? Or do multiple neural ectoderm progenitors exist, each restricted to form specific brain regions? Here our lineage tracing studies of mouse embryos support the latter model.
Chronic cerebral hypoperfusion induces venous dysfunction via EPAS1 regulation in mice - Nature Communications
Abstract Vascular dementia is the second most common form of dementia. Yet, the mechanisms by which cerebrovascular damage progresses are insufficiently understood. Here, we create bilateral common carotid artery stenosis in mice, which effectively impairs blood flow to the brain, a major cause of the disease.
The placenta as a cradle, but not source, of blood?
Every day, the body produces billions of new blood and immune cells to replace those lost to daily attrition. Manufacturing of new blood and immune cells occurs at a vast scale and an unprecedented pace, and is fueled by blood-forming hematopoietic stem cells (HSCs) [1]. As such, a timeless question in developmental biology concerns how and whence HSCs arise in the embryo [2]. Namely, how is the foundation of the future blood and immune system laid down during early development?
Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells - Nature Structural & Molecular Biology
Abstract Pioneer transcription factors (PTFs) possess the unique capability to access closed chromatin regions and initiate cell fate changes, yet the underlying mechanisms remain elusive. Here, we characterized the single-molecule dynamics of PTFs targeting chromatin in living cells, revealing a notable ‘confined target search’ mechanism.
TMX1, a disulfide oxidoreductase, is necessary for T cell function through regulation of CD3zeta
Abstract T cell-targeted therapies are commonly used to manage T cell hyperactivity in autoimmune disorders, graft-versus-host diseases (GVHD), and transplant rejections. However, many patients experience significant side effects or inadequate responses to current treatments, highlighting the urgent need for alternative strategies.
Reshaping Waddington’s developmental landscape - Nature Reviews Genetics
Imagine 2004, prior to the advent of induced pluripotent stem cells (iPS cells) and the realization that cellular identity is a tabula rasa that can be rewritten at will. It was widely accepted that once terminally differentiated cells were born, their identity — be it a brain, bone or blood cell — was fixed and immutable.
Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification - Nature Communications
Abstract Generating primordial germ cell-like cells (PGCLCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but often entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days. We use our simplified differentiation platform and single-cell RNA-sequencing to achieve further insights into PGCLC specification.
Building human artery and vein endothelial cells from pluripotent stem cells, and enduring mysteries surrounding arteriovenous development
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A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production - Nature Communications
Abstract Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types or control cell fate remains unknown. Here, employing quantitative mass spectrometry during human embryonic stem cell differentiation, we identify dozens of ribosome composition changes underlying cell fate specification.
Bridging naïve and primed pluripotency
Pluripotent cells generate all types of cells in the body and have largely been classified dichotomously into two types: naïve and primed. Arguing against a binary classification system, a study now discovers a unique transition state between naïve and primed pluripotency and describes the signals that control this transition. Fig. 1: A continuum of pluripotent states in the early mouse embryo. References 1. Loh, K. M., Lim, B. & Ang, L. T. Physiol. Rev. 95, 245–295 (2015). 2. Nichols, J. & Smith, A.
Live Imaging Reveals that the First Division of Differentiating Human Embryonic Stem Cells Often Yields Asymmetric Fates
The first lineage option that pluripotent hESCs face is to differentiate into ectoderm or the primitive streak (Murry and Keller, 2008xDifferentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Murry, C.E. and Keller, G. Cell. ; 132: 661–680 Abstract | Full Text | Full Text PDF | PubMed | Scopus (983)See all ReferencesMurry and Keller, 2008) (Figure 1Figure 1A).
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