Telomere regulation in pluripotent stem cells

Abstract

Pluripotent stem cells (PSCs) have the potential to produce any types of cells from all three basic germ layers and the capacity to self-renew and proliferate indefinitely in vitro. The two main types of PSCs, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), share common features such as colony morphology, high expression of Oct4 and Nanog, and strong alkaline phosphatase activity. In recent years, increasing evidences suggest that telomere length represents another important internal factor in maintaining stem cell pluripotency. Telomere length homeostasis and its structural integrity help to protect chromosome ends from recombination, end fusion, and DNA damage responses, ensuring the divisional ability of mammalian cells. PSCs generally exhibit high telomerase activity to maintain their extremely long and stable telomeres, and emerging data indicate the alternative lengthening of telomeres (ALT) pathway may play an important role in telomere functions too. Such characteristics are likely key to their abilities to differentiate into diverse cell types in vivo. In this review, we will focus on the function and regulation of telomeres in ESCs and iPSCs, thereby shedding light on the importance of telomere length to pluripotency and the mechanisms that regulate telomeres in PSCs.

Aging Effects on Cardiac Progenitor Cell Physiology

“…In most cell types, the two mechanisms involved in the preservation of telomere homeostasis, that is, telomerase activity and ALT, appear to be mutually exclusive. However, the ALT and telomerase pathways may coexist during reprogramming of induced pluripotent stem cells (146). Moreover, in embryonic stem cells, the ALT-related proteins, α-thalassemia mental retardation X-linked and the histone-H3 variant (H3.3), colocalize with telomeres within the promyelocitic leukemia (PML) bodies (63,157,232).…”

The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance

“…32 Control of telomere length is an intricate process involving many factors. As previously reviewed, 19 mESCs and miPSCs control telomere length largely by modulating telomeric epigenetics and regulation by several proteins, including ZSCAN4, 51,[54][55][56] ATRX, 54,55 RIF1, 56 TRF1 52,57 TPP1 and other shelterin complex components. 52,58 Increased telomere length, as part of the establishment of the pluripotent epigenome, occurs only after multiple passages, and is accomplished through epigenetic modifications of histones and subtelomeric DNA methylation.…”

“…As such, human (h)ESCs are capable of being passaged over 120 times with no decrease in telomerase activity, telomere length and pluripotency potential. 18 Several recent reviews [19][20][21] have highlighted different mechanisms by which telomeres and TERT are affected by pluripotency. These discussions tend to be singularly focused with pluripotency acting as an effector.…”

The rising young scientist stars in China

“…He published several influential research articles in journals Molecular Cell , Stem Cells , Aging Cell , Fertility and Sterility , and overviewed “telomere regulation in pluripotent stem cells” for Protein & Cell in 2014 (Huang et al, 2014). He was selected in the Young Talents of Guangdong Province for “thousand, hundred and ten excellent” Special Program, Pearl River Nova of Guangzhou, and also won the “Stem Cell Young Investigator Award” of Chinese Society for Stem Cell Biology.…”