Current Stem Cell Reports最新文献

Purpose of review: In Utero Hematopoietic Cellular Transplantation (IUHCT) is a promising intervention for the non-toxic treatment of congenital disease that hinges on the assumption of fetal immunologic immaturity and an inability to reject a hematopoietic allograft. However, clinical IUCHT has failed except in cases where the fetus is severely immunocompromised. The current review examines recent studies of engraftment barriers stemming from either the fetal or maternal immune system.

Recent findings: New reports have illuminated roles for maternal humoral and cellular immunity and fetal innate cellular immunity in the resistance to allogeneic IUHCT. These experimental findings have inspired new approaches to overcome these barriers. Despite these advances, postulates regarding a maternal immune barrier to IUHCT provide an inadequate explanation for the well-documented clinical success only in the treatment of fetal immunodeficiency with normal maternal immunity.

Summary: Characterization of the maternal and fetal immune response to allogeneic IUHCT provides new insight into the complexity of prenatal tolerance. Future work in this area should aim to provide a unifying explanation for the observed patterns of success and failure with clinical IUHCT.

Purpose of review: Hematopoiesis is an ordered developmental process that requires dynamic regulation to warrant proper response to physiological challenges and prevent malignancies. Long noncoding RNAs are emerging as key, multi-faceted regulators of gene expression. This review explores the function of lncRNAs in the control of HSC homeostasis and hematopoietic differentiation.

Recent findings: Multiple lncRNAs have been implicated in maintaining HSC stemness and enabling progenitors to carry out the correct programs of lineage differentiation. Specific lncRNAs have been identified that regulate the differentiation of multipotent progenitors into terminally differentiated blood cells. These lncRNAs predominantly act by assisting master regulators that drive specific differentiation programs, either by enhancing or repressing the transcription of particular genomic loci.

Summary: Long noncoding RNAs contribute to the correct differentiation and maturation of various hematopoietic lineages by assisting with the activation of transcriptional programs in a time- and cell-dependent manner.

Purpose of review: This review summarizes the role of hypoxia and hypoxia-inducible factors (HIFs) in the regulation of stem cell biology, specifically focusing on maintenance, differentiation, and stress responses in the context of several stem cell systems. Stem cells for different lineages/tissues reside in distinct niches, and are exposed to diverse oxygen concentrations. Recent studies have revealed the importance of the hypoxia signaling pathway for stem cell functions.

Recent findings: Hypoxia and HIFs contribute to maintenance of embryonic stem cells, generation of induced pluripotent stem cells, functionality of hematopoietic stem cells, and survival of leukemia stem cells. Harvest and collection of mouse bone marrow and human cord blood cells in ambient air results in fewer hematopoietic stem cells recovered due to the phenomenon of Extra PHysiologic Oxygen Shock/Stress (EPHOSS).

Summary: Oxygen is an important factor in the stem cell microenvironment. Hypoxia signaling and HIFs play important roles in modeling cellular metabolism in both stem cells and niches to regulate stem cell biology, and represent an additional dimension that allows stem cells to maintain an undifferentiated status and multilineage differentiation potential.

Purpose of the review: Blood specification is a highly dynamic process, whereby committed hemogenic endothelial cells (ECs) progressively transdifferentiate into multipotent, self-renewing hematopoietic stem cells (HSCs). Massive changes in gene expression must occur to switch cell identity, however the factors that mediate such an effect were a mystery until recently. This review summarizes the higher-order mechanisms involved in endothelial to hematopoietic reprogramming identified thus far.

Recent findings: Accumulating evidence from mouse and zebrafish studies reveal that numerous chromatin-modifying (epigenetic) and RNA-modifying (epitranscriptomic) factors are required for the formation of HSCs from hemogenic endothelium. These genes function throughout the endothelial-hematopoietic transition, suggesting a dynamic interplay between 'epi'-machineries.

Summary: Epigenetic and epitranscriptomic regulation are key mechanisms for reshaping global EC gene expression patterns to those that support HSC production. Future studies that capture modification dynamics should bring us closer to a complete understanding of how HSCs transition from hemogenic endothelium at the molecular level.

Purpose of review: The '14-day rule', which limits research on human embryos to the first 14 days after fertilisation, has long been a pillar of regulation in this contested area. Recently, advances in developmental biology have led to calls to rethink the rule and its application. In this paper, I address the question of whether the 14-day rule should be replaced and, if so, how.

Recent findings: The two lines of research that have prompted this question are new techniques enabling culture of embryos at least up to 14 days and patterning experiments with pluripotent cells suggesting that they might form embryo-like structures. I consider each of these in relation to the foundations and function of the rule to examine whether they warrant change.

Summary: I argue that the 14-day rule for embryo research should be open to change, but that this possibility must be addressed through early and thorough discussion involving a wide range of publics and other stakeholders.