Biology subjects

Ko, T.-M.

Publications and source records attributed to Ko, T.-M..

2 recordsLinked to original sources

bioRxiv2022

Comparative single-cell profiling reveals distinct cardiac resident macrophages essential for zebrafish heart regeneration

Zebrafish exhibit a robust ability to regenerate their hearts following injury, and the immune system plays a key role in this process. We previously showed that delaying macrophage recruitment by clodronate liposome (CL) treatment compromises neutrophil resolution and heart regeneration, even when the infiltrating macrophage number was restored within the first-week post injury (Lai et al., 2017). Here, we examined the molecular mechanisms underlying the cardiac repair of regenerative PBS-control hearts vs. non-regenerative CL-treated hearts. Bulk transcriptomic analyses revealed that CL-treated hearts exhibited disrupted inflammatory resolution and energy metabolism during cardiac repair. Temporal single-cell profiling of inflammatory cells in regenerative vs. non-regenerative conditions further identified heterogenous macrophages and neutrophils with distinct infiltration dynamics, gene expression, and cellular crosstalk. Among them, two residential macrophage subpopulations were enriched in regenerative hearts and barely recovered in non-regenerative hearts. Early CL treatment at 8 days or even 1 month before cryoinjury led to the depletion of resident macrophages without affecting the circulating macrophage recruitment to the injured area. Strikingly, these resident macrophage-deficient zebrafish still exhibited compromised neovascularization and scar resolution. Our results characterized the inflammatory cells of the zebrafish injured hearts and identified key resident macrophage subpopulations prerequisite for successful heart regeneration.

developmental biology↗

bioRxiv2020

Population-based Carrier Screening and Prenatal Diagnosis of Fragile X Syndrome in East Asian Populations

Identification of carriers of fragile X syndrome (FXS) with the subsequent prenatal diagnosis, and knowledge of FXS-associated genetic profiles are essential for intervention in specific populations. We report the results of carrier screening of 39,458 East Asian adult women and prenatal diagnosis from 87 FXS carriers. The prevalence of FXS carriers and incidence of full mutation fetuses in carrier pregnancies were found to be 1/556 and 11.0%, respectively. The prevalence of FXS carriers and full mutation fetuses was estimated to be 1/581 and 1/3124 in East Asian populations, respectively. We confirmed the validity of the current threshold of CGG repeats for FMR1 categorization; the integral risks of full mutation expansion were approximately 6.0%, 43.8%, and 100% for premutation alleles with 55-74, 75-89, and [≥]90 CGG repeats, respectively. The protective effect of AGG interruption in East Asian populations was validated, which is important in protecting premutation alleles with 75-89 CGG repeats from full mutation expansion. Lastly, family history was shown not an effective indicator for FXS carrier screening in East Asian populations and population-based screening was more cost-effective. This study provides an insight into the largest carrier screening and prenatal diagnosis for FXS in East Asian populations to date. The FXS-associated genetic profiles of East Asian populations are delineated and population-based carrier screening is shown to be promising for FXS intervention.

genetics↗