title: Hematopoietic stem cell lineage specification.
abstract: Hematopoietic stem cells (HSCs) possess two fundamental characteristics, the capacity for self-renewal and the sustained production of all blood cell lineages. The fine balance between HSC expansion and lineage specification is dynamically regulated by the interplay between external and internal stimuli. This review introduces recent advances in the roles played by the stem cell niche, regulatory transcriptional networks, and metabolic pathways in governing HSC self-renewal, commitment, and lineage differentiation. We will further focus on discoveries made by studying hematopoiesis at single-cell resolution.
  
  
  
  HSCs require the support of an interactive milieu with their physical position within the perivascular niche dynamically regulating HSC behavior. In these microenvironments, transcription factor networks and nutrient-mediated regulation of energy resources, signaling pathways, and epigenetic status govern HSC quiescence and differentiation. Once HSCs begin their lineage specification, single-cell analyses show that they do not become oligopotent but rather, differentiate directly into committed unipotent progenitors.
  
  
  
  The diversity of transcriptional networks and metabolic pathways in HSCs and their downstream progeny allows a high level of plasticity in blood differentiation. The intricate interactions between these pathways, within the perivascular niche, broaden the specification of HSCs in pathological and stressed conditions.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR5535, Université de Montpellier, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Pouzolles
authors.forename: Leal
authors.initials: L
authors.lastname: Oburoglu
authors.forename: Naomi
authors.initials: N
authors.lastname: Taylor
authors.forename: Valérie S
authors.initials: VS
authors.lastname: Zimmermann
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D059010:Single-Cell Analysis; D055153:Stem Cell Niche; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors