Approaches towards Elucidating the Metabolic Program of Hematopoietic Stem/Progenitor Cells

Cells. 2022 Oct 11;11(20):3189. doi: 10.3390/cells11203189.

Abstract

Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate (ATP), which is necessary for various cellular functions. Metabolites not only provide stem/progenitor cells with nutrients for ATP and building block generation but are also utilized for protein modification and epigenetic regulation to maintain cellular characteristics. In recent years, the metabolic programs of tissue stem/progenitor cells and their underlying molecular mechanisms have been elucidated using a variety of metabolic analysis methods. In this review, we first present the advantages and disadvantages of the current approaches applicable to the metabolic analysis of tissue stem/progenitor cells, including HSCs and HPCs. In the second half, we discuss the characteristics and regulatory mechanisms of HSC metabolism, including the decoupling of ATP production by glycolysis and mitochondria. These technologies and findings have the potential to advance stem cell biology and engineering from a metabolic perspective and to establish therapeutic approaches.

Keywords: bone marrow environment; hematopoietic progenitor cells; hematopoietic stem cells; metabolome analysis; single cell metabolic analysis; stem cell metabolism; tracer analysis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bone Marrow / metabolism
  • Epigenesis, Genetic*
  • Glycolysis
  • Hematopoietic Stem Cells* / metabolism

Substances

  • Adenosine Triphosphate

Grants and funding

This research was funded in part by KAKENHI grants from MEXT/JSPS (JP19K17847, JP21K08431 to H.K.; JP18H02845, JP20K21621, JP21H02957, JP22K19550, JP20H00509 to K.T.), AMED grants (JP18ck0106444, JP18ae0201014, JP20bm0704042, JP20gm1210011 to K.T.), grants from the National Center for Global Health and Medicine (29-1015, 20A1010 to H.K.; 26-001, 21A2001 to K.T.), the Takeda Science Foundation (to K.T.), and the MEXT Joint Usage/Research Center Program at the Advanced Medical Research Center, Yokohama City University (to K.T.).