Biomedical subjects

Sai Ma

Publications and source records attributed to Sai Ma.

3 recordsLinked to original sources

PubMed2026

Deoxyribonucleic acid methylation abnormalities at imprinted loci in oligospermic and azoospermic men.

OBJECTIVE: To assess deoxyribonucleic acid (DNA) methylation at imprinted and repetitive genomic regions in ejaculated and testicular sperm from men with oligospermia, azoospermia, and those undergoing vasectomy reversal (VR), compared with fertile controls. DESIGN: Observational case-control study. SUBJECTS: Samples were obtained from 68 men, including 29 infertile men (18 oligospermic [5-15 million/mL], 11 severely oligospermic [<5 million/mL]) and 20 fertile controls with confirmed natural conceptions. Testicular tissue was collected from 11 azoospermic men (7 obstructive azoospermia [OA], 4 nonobstructive azoospermia [NOA]) and 8 men with prior paternity undergoing VR. EXPOSURE: Sperm DNA methylation at four imprinted genes (H19, GTL2, MEST, and LIT1) and one repetitive element (LINE1). MAIN OUTCOME MEASURES: Methylation levels at CpG sites determined by bisulfite pyrosequencing. RESULTS: The H19 was significantly hypomethylated only in severe oligospermia compared with fertile controls, whereas other groups showed nonsignificant trends with overlapping distributions. In contrast, MEST was significantly hypermethylated in oligospermic, azoospermic, and VR groups compared with fertile controls. No significant differences were observed for GTL2, LIT1, or LINE1. CONCLUSION: The DNA methylation abnormalities in sperm are locus-specific and vary across infertility phenotypes. MEST alterations were consistent across groups, whereas H19 changes were limited to severe oligospermia. Similar methylation patterns in testicular sperm from azoospermic and VR groups suggest that epigenetic alterations may reflect the testicular environment or obstruction, or differences between testicular and ejaculated sperm.

Humans↗

PubMed2025

A single-cell spatial transcriptomic census of human skin anatomy.

The skin is the largest human organ and a site of significant disease burden, yet its cellular and molecular organization across the body are largely undefined. Here, we construct a spatially-resolved single-cell atlas of 1.2 million cells from normal adult human skin to localize 45 cell types across 15 anatomic sites. We define principles of organ-wide cell composition, including axes of cell diversity and specialization, and distinguish site-enriched cell types. Each body site is comprised of 10 multicellular neighborhoods that define cell-cell communication. Notably, we identify a perivascular neighborhood enriched for immune-stromal crosstalk with features resembling a homeostatic immune niche similar to skin-associated lymphoid tissue. Finally, mapping these neighborhoods onto skin disease reveals pathogenic neighborhood disruptions, including pan-disease immune alterations in the perivascular neighborhood. We present a framework charting the skin's multiscale spatial organization across a molecular to macroanatomic scale. This work advances our understanding of organ-wide skin cellular organization and communication, and its architectural disruption in disease.

Journal Article↗

PubMed2025

HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.

Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.

Hepatocytes↗