Both alleles of PSF1 are required for maintenance of pool size of immature hematopoietic cells and acute bone marrow regeneration

Abstract

Hematopoietic stem cells (HSCs) have a very low rate of cell division in the steady state; however, under conditions of hematopoietic stress, these cells can begin to proliferate at high rates, differentiate into mature hematopoietic cells, and rapidly reconstitute ablated bone marrow (BM). Previously, we isolated a novel evolutionarily conserved DNA replication factor, PSF1 (partner of SLD5-1), from an HSCspecific cDNA library. In the steady state,

Balancing dormant and self-renewing hematopoietic stem cells

“…The molecular basis of the HSC response to the chemotherapeutic drug 5-FU involves activation of proliferation and modification of adhesion [11]. In addition, the evolutionarily conserved DNA replication factor PSF1, is required for regeneration after 5-FU treatment and to maintain HSC numbers [55].…”

PSF1, a DNA Replication Factor Expressed Widely in Stem and Progenitor Cells, Drives Tumorigenic and Metastatic Properties

“…Quantitative reverse transcription-PCR (RT-PCR) was done as previously described (14). The primer sets were described in Supplementary Materials and Methods.…”

“…For immunocytochemistry, anti-PSF1(14), anti-bromodeoxyuridine (BrdUrd) (Zymed Laboratories), anti-β-tubulin (Sigma), anti-CENP-A (MBL), and anti-survivin (Chemicon International, Inc.) antibodies were used as previously described (14).…”

“…Moreover, we reported that PSF1 is strongly expressed in different immature cell lineages, such as cells in the inner cell mass during early embryogenesis as well as spermatogonia and hematopoietic stem cells after birth (12)(13)(14). Loss of PSF1 led to embryonic lethality around the implantation stage caused by the inability of cells of the inner cell mass to proliferate (12).…”

CD44 Expressed on Cancer-Associated Fibroblasts Is a Functional Molecule Supporting the Stemness and Drug Resistance of Malignant Cancer Cells in the Tumor Microenvironment

“…PSF1 is a member of the GINS (Go-IchiNi-San) complex associated with the formation of the DNA replication fork. We found that PSF1 is required for acute proliferation of normal stem cells such as epiblasts in the embryo and hematopoietic stem cells in bone marrow [17,18]. PSF1 expression visualized by enhanced green fluorescent protein (EGFP) under the transcriptional control of the PSF1 promoter in lung cancer cells (LLC-PSF1p-EGFP cells) indicated that a high level of PSF1 transcriptional activity in cancer cells (PSF1-EGFP high ) derived from tumors in vivo was associated with a higher invasive, tumorigenic, and metastatic activity compared with PSF1-EGFP low cancer cells.…”